Table of Contents
Overview
Definition and Scope
Mechanobiology is an emerging multidisciplinary field that integrates concepts from cell and developmental biology, bioengineering, and biophysics to explore how mechanical forces influence biological systems. It encompasses the study of how cells, tissues, and organs sense and respond to mechanical cues, thereby regulating various biological processes such as development, differentiation, physiology, and disease.[3.1] The field focuses on understanding the interplay between mechanical forces and biological responses, particularly how changes in the mechanical properties of cells and tissues contribute to physiological functions and pathological conditions.[4.1] A significant aspect of mechanobiology is the concept of mechanotransduction, which refers to the molecular mechanisms by which cells detect and respond to mechanical signals. This understanding is crucial, as it has been shown that alterations in cell mechanics, extracellular matrix structure, or mechanotransduction pathways can play a role in the development of various diseases, including atherosclerosis, fibrosis, asthma, osteoporosis, heart failure, and cancer.[4.1] Research in mechanobiology also emphasizes the importance of cellular connections and the extracellular environment, which provide mechanical coupling between neighboring cells and facilitate tissue organization. By examining mechanobiology at molecular, cellular, and tissue levels, researchers aim to uncover the effects of mechanical forces on biological systems and develop innovative technologies to enhance health and agricultural practices.[5.1] The interdisciplinary nature of mechanobiology fosters collaboration among experts in diverse fields, including physics, chemistry, mathematics, and engineering, to advance the understanding and application of mechanobiological principles.[3.1]Importance in Biological Processes
Mechanobiology plays a crucial role in understanding how cells and tissues develop and respond to mechanical forces, which is essential for both basic research and clinical applications. This field investigates how cells produce, sense, and respond to mechanical stimuli, thereby influencing their shape and function during development and disease.[7.1] The integration of mechanobiology into clinical practice is expected to evolve significantly, particularly in the development of targeted therapies for diseases such as cancer and cardiovascular conditions.[6.1] In cancer, for instance, mechanical alterations—such as changes in structural properties, morphology, and stiffness of both cells and their extracellular environment—are critical during all stages of cancer initiation and metastasis.[8.1] These irregular mechanical changes can affect the survival of cancer cells in circulation and their ability to invade and colonize secondary sites.[8.1] Furthermore, the emerging field of cardio-oncology highlights the interplay between cancer therapies and cardiovascular health, emphasizing the need for mechanobiological insights to mitigate potential complications arising from treatment.[10.1] The application of artificial intelligence (AI) in mechanomedicine further enhances the understanding of mechanobiology by improving the accuracy of biomechanical characterizations and enabling early disease detection through mechanodiagnosis.[9.1] AI also facilitates personalized treatment strategies by optimizing mechanotherapy, which targets biomechanical features and mechanobiological markers based on real-time patient data.[9.1]In this section:
History
Key Developments in Mechanobiology
Mechanobiology has emerged as a significant field of study over the past decade, focusing on the role of mechanical forces in biological processes. The discipline is rooted in the concept of "cell mechanosensing," which is central to understanding how cells perceive and respond to mechanical stimuli.[47.1] Integral mechanobiology has been proposed as a new branch of science that harmonizes the advances of genetics and molecular biology with the study of mechanical forces in living organisms.[48.1] The field examines how physical forces and changes in the mechanical properties of cells and tissues contribute to various biological phenomena, including development, cell differentiation, and disease.[49.1] For instance, mechanical forces such as joint movement and compressive loads on cartilage during exercise are critical to understanding physiological responses and the development of diseases like atherosclerosis and cancer.[50.1] Key milestones in mechanobiology include the recognition of mechanotransduction as a critical regulator of biological processes, which involves the conversion of mechanical signals into biochemical responses.[52.1] Research has highlighted the importance of specialized proteins, such as ion channels, in mediating mechanotransduction, thereby influencing cellular activities and metabolism.[53.1] The RhoA signaling pathway has also been identified as central to mechanotransduction, regulating the actin cytoskeleton's response to mechanical forces.[55.1] The historical development of mechanobiology has been shaped by interdisciplinary insights from fields such as structural engineering and biomechanics, which have contributed to our understanding of the extracellular matrix and tissue mechanics.[59.1] Early studies laid the groundwork for current research, emphasizing the significance of mechanical forces in cellular behavior and tissue development.[60.1] As mechanobiology continues to evolve, it is poised to revolutionize our understanding of cell growth, differentiation, and apoptosis, with the potential for significant biomedical innovations.[56.1]Recent Advancements
Technological Innovations
Recent advancements in mechanobiology have led to significant technological innovations, particularly in the fields of biomaterials and agricultural practices. Engineered biomaterials have emerged as crucial components in tissue engineering, providing extracellular microenvironments with well-controlled physical properties. These properties enable researchers to study their effects on cellular behaviors, thereby enhancing the integration of engineered biomaterials with existing therapeutic strategies.[92.1] Furthermore, hydrogels can be engineered to present therapeutic factors in a controlled manner, allowing for mechanical constraints that influence the behavior of hydrogel particles.[93.1] In the context of cell-based therapies, optimizing the mechanical environment of exogenous cells within biomaterials is essential for facilitating tissue regeneration. This has led to the development of workflows for the inverse design of mechanobiomaterials, which aim to tailor these environments to improve therapeutic outcomes.[94.1] The translation of mechanobiological research into clinical applications presents several challenges. A recent panel discussion highlighted the importance of defining translational research within mechanobiology and the current landscape of such research. It emphasized the need for effective strategies to move laboratory discoveries into broader applications, including the development of technology products that can impact clinical care.[96.1] In agricultural practices, advancements in mechanobiology are being leveraged to improve crop resilience and productivity. Recent innovations include high-throughput phenotyping and AI technologies that facilitate real-time measurement of crop traits under various environmental conditions, such as heat stress.[108.1] Additionally, the integration of crop wild relatives, pangenomes, and scalable gene editing strategies are being explored to enhance crop climate resilience.[110.1] These technological innovations underscore the potential of mechanobiology to drive significant improvements in both healthcare and agriculture.Current Research Trends
Current research in mechanobiology is increasingly focused on understanding the intricate relationships between mechanical forces and biological systems, particularly at the cellular and tissue levels. This field examines how physical forces and the mechanical properties of cells and tissues contribute to various biological processes, including development, cell differentiation, physiology, and disease.[89.1] A significant challenge within mechanobiology is elucidating the mechanisms of mechanotransduction, which refers to how cells sense and respond to mechanical signals.[89.1] Recent advancements have highlighted the role of the extracellular matrix (ECM) in mediating cellular responses to mechanical stimuli. Researchers have developed biomaterial-based platforms that mimic synthetic ECMs, allowing for precise control over cellular behaviors by adjusting mechanical properties.[91.1] This approach has implications for therapeutic strategies, particularly in regenerative medicine, where understanding the mechanical cues that govern stem cell differentiation is crucial.[99.1] Emerging studies indicate that mechanical factors can spatially direct differentiation decisions in stem cells, influencing their potential for tissue regeneration.[99.1] Moreover, mechanobiology is proving to be a vital area of research in cancer biology. The mechanical properties of cancer cells and their tumor microenvironment (TME) significantly affect tumor development, progression, and drug resistance.[105.1] Investigations into cancer cell mechanobiology aim to uncover how mechanical features influence cancer cell invasion and metastasis, potentially leading to the identification of new diagnostic biomarkers and therapeutic targets.[103.1] The integration of mechanobiology into therapeutic strategies is expected to enhance treatment efficacy for various conditions, including cancer and cardiovascular diseases, by addressing the physical barriers that impact treatment outcomes.[104.1]In this section:
Mechanotransduction
Molecular Mechanisms
Mechanotransduction involves various molecular mechanisms that enable cells to convert mechanical stimuli into biochemical signals, influencing cellular behavior and adaptation. A fundamental aspect of this process is the role of integrins, which are transmembrane proteins that facilitate cell-matrix adhesion. Integrins not only act as mechanotransducers but also transmit forces to other cellular components, thereby playing a crucial role in the mechanotransduction pathways.[140.1] They connect the extracellular matrix (ECM) to the cytoskeleton through adapter molecules such as talin and vinculin, allowing for bidirectional signaling that regulates cellular responses to mechanical forces.[142.1] The cytoskeleton, composed of actin filaments and other structural proteins, is integral to mechanotransduction. It senses mechanical stimuli such as ECM stiffness and shear stress, converting these signals into intracellular chemical signals.[145.1] For instance, endothelial cells utilize their cytoskeletal components to respond to hemodynamic shear stress, which is critical for maintaining endothelial homeostasis and influencing various cellular events, including proliferation and inflammatory responses.[150.1] Additionally, specific signaling pathways are activated in response to mechanical forces. For example, shear stress can trigger calcium signaling through purinergic receptors, leading to the influx of extracellular calcium and subsequent intracellular changes.[148.1] This mechanotransduction pathway is essential for endothelial cell function and can influence gene expression and cellular phenotype.[149.1] In the context of tissue engineering, understanding these molecular mechanisms is vital. The interaction of stem cells with biomechanical cues can be manipulated through the design of biomaterials that mimic the mechanical properties of native tissues. This approach enhances the effectiveness of regenerative medicine strategies by promoting appropriate cellular responses to mechanical stimuli.[151.1] Overall, the intricate interplay between integrins, cytoskeletal components, and signaling pathways underscores the complexity of mechanotransduction and its significance in both health and disease.[134.1]Role in Disease and Physiology
Mechanotransduction plays a critical role in various diseases and physiological processes, particularly in osteoarthritis (OA) and cardiovascular diseases (CVD). In OA, excessive mechanical stress is a significant factor in the initiation and progression of the disease, leading to articular cartilage degradation.[138.1] This understanding has prompted research into therapies that target mechanotransduction pathways to mitigate cartilage loss and alleviate pain. For instance, a phase Ib study demonstrated that intra-articular injection of sprifermin resulted in a statistically significant dose-dependent reduction in the loss of total femorotibial cartilage thickness in patients with symptomatic knee OA compared to a placebo after 12 months.[135.1] Moreover, mechanotransduction is essential in cardiovascular health, where hemodynamic shear stress—the frictional force exerted by blood flow on the endothelium—mediates vascular homeostasis.[137.1] Disturbances in this flow can lead to conditions such as atherosclerosis, which preferentially develops at arterial branches and curvatures.[137.1] The shared risk factors and molecular mechanisms between OA and CVD highlight the potential for therapeutic strategies that leverage mechanotransduction to address both conditions.[139.1] Recent advancements in understanding mechanotransduction have also opened avenues for innovative clinical applications. For example, mechanotherapy, which involves using mechanical loads to stimulate tissue repair and remodeling, has shown promise in enhancing musculoskeletal tissue repair.[159.1] This approach is supported by evidence that mechanical cues can activate pathways regulating cytoskeleton remodeling, cell proliferation, and tissue differentiation.[174.1] Such insights into the mechanotransduction processes not only inform rehabilitation practices but also enhance the development of regenerative medicine strategies, including stem cell therapy and tissue engineering.[161.1]Applications In Tissue Engineering
Strategies for Functional Tissue Design
A primary challenge in tissue engineering is to replicate both the structural and functional features of whole tissues and organs. This requires a comprehensive understanding of the complex interactions between mechanical properties and cellular behaviors, particularly how cells sense and respond to mechanical cues from their environment.[178.1] Mechanobiology plays a crucial role in this context, as it informs the design of scaffolds and biomaterials that can effectively guide cellular functions such as differentiation, proliferation, and migration.[179.1] To achieve functional tissue design, researchers are increasingly focusing on the mechanical properties of the extracellular matrix (ECM) and scaffolds. These properties significantly impact therapeutic efficacy by regulating cell behaviors.[179.1] For instance, the development of biomaterials with specific mechanical characteristics can mimic the natural mechanical environment of various tissue types, thereby influencing stem cell behavior and enhancing tissue regeneration.[181.1] Advanced strategies are being employed to provide precise spatial and temporal control of mechanical signals, which is essential for effective tissue engineering and regenerative medicine.[181.1] Moreover, the challenge of mimicking the mechanical properties of native tissues is addressed through various techniques, including additive manufacturing. This technology allows for the precise and heterogeneous deposition of biomaterials, enabling the creation of complex structures that replicate the anisotropic nature of native tissues.[192.1] The successful fabrication of microtissues that possess mechanical properties similar to those of stretchable tissues, such as muscle and tendon, is also a critical area of focus.[189.1]Challenges in Replicating Tissue Structure
Challenges in replicating tissue structure in the context of mechanobiology are significant and multifaceted. One of the primary challenges is the need to accurately mimic the extracellular matrix (ECM), which plays a crucial role in cellular mechanics and wound healing. The ECM can activate cell surface receptors and facilitate long-range mechanical interactions, making it essential for effective cell culture and tissue engineering applications. Therefore, utilizing biocompatible hydrogels or ECM mimics is desirable for culturing cells, yet achieving the right mechanical properties remains a challenge.[183.1] Moreover, skin diseases and dysfunctional wound healing present substantial healthcare challenges, with conditions such as keloids—characterized by excessive fibrosis—highlighting the complexities involved in replicating tissue structures that can withstand mechanical strain. The economic burden of these conditions, including the costs associated with overhealing in burns and trauma, underscores the urgency of developing effective therapies that can address these issues.[184.1] Research into skin biomechanics and mechanobiology has revealed that the mechanical properties of wounds significantly influence the rate and quality of healing. Understanding these properties can lead to improved therapeutic strategies aimed at enhancing wound healing and minimizing scarring. However, translating this knowledge into practical applications poses challenges, particularly in ensuring that new therapies effectively integrate mechanical forces to promote skin regeneration.[186.1] Furthermore, the process of skin wound healing is vital for re-establishing the epithelial barrier after injury or disease. Delays or aberrations in this process can increase the risk of infection and lead to patient morbidity, emphasizing the need for therapies that can replicate the natural healing environment.[187.1] Addressing these challenges is crucial for advancing the field of tissue engineering and improving clinical outcomes in wound healing.In this section:
Interdisciplinary Connections
Integration with Engineering and Physics
Mechanobiology represents a significant interdisciplinary field that integrates concepts from biology, physics, engineering, and material science to explore how biological systems respond to mechanical stimuli. This integration is crucial for understanding the fundamental processes of cellular organization, movement, growth, and interaction with their environment, which are all influenced by mechanical forces and properties.[225.1] The study of mechanobiology emphasizes the importance of mechanical cues in regulating various biological processes, including development, differentiation, and tissue repair.[224.1] By leveraging principles from physics and engineering, researchers can elucidate how cells sense and transduce mechanical signals into biochemical responses, thereby influencing cellular behavior and function.[225.1] This understanding is essential for the development of innovative therapies that can manipulate mechanical forces to induce specific biological outcomes, such as tissue regeneration or repair.[224.1] Moreover, the design of biomaterials and scaffolds that mimic the mechanical properties of natural tissues is a key area where mechanobiology intersects with engineering. The mechanical properties of these materials, such as stiffness and degradation rates, are critical for supporting cellular activity and promoting tissue integration.[236.1] Advanced biomaterials engineered with specific mechanical characteristics and bioactive ligands can significantly enhance our ability to control cell function and behavior in engineered tissues.[237.1] As mechanobiology continues to evolve, the integration of physical principles is expected to drive future research directions, particularly in the development of new therapies and materials for tissue engineering. This includes the application of artificial intelligence and machine learning to analyze complex data related to mechanical properties and cellular responses, which may lead to transformative advances in the field.[244.1] Ultimately, a comprehensive understanding of mechanobiology, supported by interdisciplinary collaboration, will facilitate the creation of more effective therapeutic strategies and biomaterials that align closely with the mechanical demands of biological systems.[243.1]Impact on Other Scientific Fields
Mechanobiology significantly influences various scientific fields, particularly in the realms of materials science, bioengineering, and tissue engineering. Recent advancements in mechanobiology have highlighted the critical role of mechanical cues in regulating cellular functions, which has implications for the development of biomaterials used in tissue engineering and regenerative medicine.[239.1] The integration of biology, biomechanics, and materials science allows for the creation of biomaterials that can proactively influence cell and tissue responses through mechanical interactions.[239.1] In tissue engineering, mechanobiology has led to innovative approaches that utilize bioreactors to apply dynamic mechanical stimulation, aiming to engineer functional soft tissue replacements and disease state models.[246.1] These bioreactors are designed to apply user-defined cyclic strains to cells and tissues in vitro, enhancing our understanding of how mechanical forces influence tissue development and healing.[248.1] Furthermore, the role of mechanical stimulation bioreactors extends beyond improving the quality of tissue-engineered constructs; they are essential for studying the basic mechanobiology of cells in a physiologically relevant manner.[247.1] The design of mechanobiomaterials is also evolving, with a focus on creating materials that can adapt and respond to the changing mechanical environment of tissues and cells.[251.1] This emerging field emphasizes the importance of material-tissue mechanical interactions and the relationship between material properties and biological responses.[252.1] By employing mathematical and physical models, researchers can optimize material properties and geometry, leading to enhanced tissue repair and regeneration.[240.1]In this section:
Future Directions
Emerging Research Areas
Emerging research areas in mechanobiology are increasingly focused on the interplay between mechanical forces and biological systems, with significant implications for health and disease. A comprehensive understanding of mechanobiology is anticipated to facilitate the development of innovative therapies that manipulate mechanical forces to induce specific biological changes, such as tissue repair and organ formation.[262.1] This field is characterized by its interdisciplinary nature, integrating principles from physics, chemistry, mathematics, and engineering to advance biological knowledge and applications.[264.1] Recent studies have highlighted the importance of mechanobiology in addressing current research gaps and proposing new theoretical advancements. These insights are crucial for expanding the application of mechanobiology in various domains, particularly in health and disease contexts.[263.1] The role of mechanical forces in cellular function has been increasingly recognized, with research demonstrating that tuning these forces can potentially cure diseases by influencing biological functions at multiple scales, from molecules to tissues.[265.1] Artificial intelligence (AI) and machine learning (ML) are emerging as transformative tools in mechanobiology research. These technologies enable advanced data analysis, predictive modeling, and automation of experimental procedures, which can enhance the understanding of mechanotransduction pathways and improve the characterization of cellular and tissue mechanics.[266.1] For instance, AI has been utilized to interpret complex biological data, leading to the identification of new biomarkers and therapeutic targets related to extracellular matrix (ECM) mechanics.[268.1] Furthermore, AI's ability to analyze cell morphology and mechanosensing capabilities is paving the way for novel cancer therapies.[268.1] The integration of AI and ML into mechanobiology also presents challenges, particularly in ensuring the accuracy and reliability of models that combine mechanistic and data-driven approaches. Addressing these challenges is essential for the successful implementation of these technologies in biological research.[271.1] Overall, the future of mechanobiology is poised for significant advancements, driven by interdisciplinary collaboration and the incorporation of cutting-edge technologies.Potential Therapeutic Applications
The integration of mechanobiology with tissue engineering and regenerative medicine is poised to significantly influence future therapeutic strategies. A comprehensive understanding of mechanotransduction mechanisms is essential for developing next-generation tissue engineering therapies that synergistically combine physical and chemical signals to direct cell fate.[283.1] This understanding will facilitate the creation of engineered platforms that can apply mechanical forces to cells in a controlled manner, promoting specific cellular responses such as proliferation, orientation, and tissue development.[285.1] Moreover, advancements in artificial intelligence (AI) are expected to enhance research capabilities in mechanobiology. AI can enable advanced data analysis, predictive modeling of mechanical properties, and automation of experimental procedures, which will provide new insights into mechanotransduction pathways.[286.1] These technological advancements will allow researchers to visualize and quantify cellular responses to mechanical stimuli, thereby improving the design of therapeutic interventions.[284.1] In the context of disease treatment, particularly for conditions like cancer and fibrosis, understanding mechanotransduction at the cellular level can inform the development of targeted therapies. Pathological tissue remodeling and fibrosis are closely regulated by mechanical forces generated through cell interactions and cytoskeletal changes.[301.1] Research indicates that the stiffness of the extracellular matrix (ECM) can modulate cancer cell mechanics and function, influencing critical disease hallmarks such as angiogenesis and metastasis.[303.1] Therefore, therapies that target the mechanical properties of the ECM may offer novel approaches to combat these diseases. Furthermore, the activation of myofibroblasts in fibrosis and tumor stroma is influenced not only by biochemical factors but also by the physical microenvironment, including matrix stiffness.[304.1] This highlights the potential for therapies that address both biochemical and mechanical aspects of disease progression. By leveraging insights from mechanobiology, future therapeutic strategies can be developed to more effectively manage diseases characterized by altered mechanical environments.[302.1]In this section:
References
[3] Mechanobiology: A New Frontier in Biology - PMC - PubMed Central (PMC) — Mechanobiology: A New Frontier in Biology - PMC doi: 10.3390/biology10070570 Mechanobiology is the study of how biological components such as cells, tissues, and organs can sense and respond to mechanical cues to regulate numerous biological processes, including development, differentiation, physiology, and diseases . This Special Issue will help shed light on advances in biology through interdisciplinary integration of physics, chemistry, mathematics, and engineering, focusing on the state-of-the-art knowledge of mechanobiology and the application of mechanobiology principles. 4.Jansen K.A., Donato D.M., Balcioglu H.E., Schmidt T., Danen E.H., Koenderink G.H. A guide to mechanobiology: Where biology and physics meet. 11.Sun Y., Kim D.-H., Simmons C.A. Integrative Mechanobiology: Micro- and Nano-Techniques in Cell Mechanobiology.
[4] Mechanobiology - Wikipedia — It focuses on how physical forces and changes in the mechanical properties of cells and tissues contribute to development, cell differentiation, physiology, and disease. The movement of joints, compressive loads on the cartilage and bone during exercise, and shear pressure on the blood vessel during blood circulation are all examples of mechanical forces in human tissues. A major challenge in the field is understanding mechanotransduction—the molecular mechanisms by which cells sense and respond to mechanical signals. While medicine has typically looked for the genetic and biochemical basis of disease, advances in mechanobiology suggest that changes in cell mechanics, extracellular matrix structure, or mechanotransduction may contribute to the development of many diseases, including atherosclerosis, fibrosis, asthma, osteoporosis, heart failure, and cancer.
[5] What Is Mechanobiology? - Center for Engineering MechanoBiology — At the tissue level, connections between neighboring cells and between cells and their extracellular environment, the cell wall in plants and the extracellular matrix (ECM) in animals, are important to provide mechanical coupling between neighboring cells and facilitate cellular organization into tissues as a continuous response element. By studying mechanobiology at the molecular, cellular and tissue levels, researchers in the Center for Engineering MechanoBiology (CEMB) can better understand the effects of mechanical forces on biological systems and develop new technologies to improve health and agriculture. We foster collaboration among researchers from a wide variety of expertise, including cell biology, developmental biology, bioengineering, materials science, biophysics, and mechanical engineering, to facilitate new discoveries and technologies in mechanobiology. Learn More About Mechanobiology Research at the CEMB
[6] Thinking multi-scale to advance mechanobiology - Nature — By unravelling the web of complexity inherent to mechanobiology, the potential of this field to contribute to the future directions of basic research and clinical applications is promising.
[7] Mechanobiology: Shaping the future of cellular form and function — Mechanobiology—the field studying how cells produce, sense, and respond to mechanical forces—is pivotal in the analysis of how cells and tissues take shape in development and disease. As we venture into the future of this field, pioneers share their insights, shaping the trajectory of future research and applications.
[8] Mechanobiology in oncology: basic concepts and clinical prospects — The latter steps of disease involve survival of cancer cells in blood circulation (Figure 1D) (Aceto et al., 2015; Reymond et al., 2013) and exit from the vessels at distal tissues (a process known as extravasation) to ultimately invade and colonize in the secondary sites (Figure 1E) (Nguyen et al., 2009). In addition to a number of unique genetic and biochemical factors associated with metastasis (Suresh, 2007; Kumar and Weaver, 2009; Wirtz et al., 2011), irregular mechanical alterations such as structural, morphological and stiffness changes, in both cells and the extracellular environment, play a significant role during all stages of cancer initiation and dissemination.
[9] Invited Review for 20th Anniversary Special Issue of PLRev "AI for ... — This review explores how AI impacts mechanomedicine across four key aspects, i.e., biomechanics, mechanobiology, mechanodiagnosis, and mechanotherapy. AI improves the accuracy of biomechanical characterizations and models, deepens the understanding of cellular mechanotransduction pathways, and enables early disease detection through mechanodiagnosis. In addition, AI optimizes mechanotherapy that targets biomechanical features and mechanobiological markers by personalizing treatment strategies based on real-time patient data. In this review, we aim to provide a comprehensive discussion on the pivotal role of AI in advancing mechanomedicine, with a specific focus on four key aspects, i.e., biomechanics (Section 2), mechanobiology (Section 3), mechanodiagnosis (Section 4), and mechanotherapy (Section 5). Biomechanics forms the foundation of mechanomedicine by exploring how mechanical forces regulate biological processes across cellular to tissue levels.
[10] Cardio-Oncology: How New Targeted Cancer Therapies and Precision ... — The field of cardio-oncology (the cardiovascular-focused study and care of cancer patients) has emerged due to the increasing recognition that traditional and novel mechanism-based therapies to treat cancer also have the potential to affect the cardiovascular system and cause clinical complications; indeed, these complications represent a
[47] [Short history on the birth of mechanobiology.] - Europe PMC — Mechanobiology deals with a wide variety of objectives, including molecules, cells, tissues, organs and individuals, in which "Cell Mechanosesing" forms the core concept. Starting with a definition of cell mechanosensing, this short review gives an outline of the history of mechanobiology and perspectives on the mechanobiology in the near future.
[48] Prerequisites for the Formation of Modern Mechanobiology — This suggests the formation of integral mechanobiology, a new branch of science that is aimed at studying the organizing role of mechanical forces and stresses in the development and functioning of living organisms, which accepts and harmoniously complements the advances of genetics and molecular biology.
[49] Mechanobiology - Wikipedia — It focuses on how physical forces and changes in the mechanical properties of cells and tissues contribute to development, cell differentiation, physiology, and disease. The movement of joints, compressive loads on the cartilage and bone during exercise, and shear pressure on the blood vessel during blood circulation are all examples of mechanical forces in human tissues. A major challenge in the field is understanding mechanotransduction—the molecular mechanisms by which cells sense and respond to mechanical signals. While medicine has typically looked for the genetic and biochemical basis of disease, advances in mechanobiology suggest that changes in cell mechanics, extracellular matrix structure, or mechanotransduction may contribute to the development of many diseases, including atherosclerosis, fibrosis, asthma, osteoporosis, heart failure, and cancer.
[50] Mechanobiology: A New Frontier in Biology - PMC — Mechanobiology: A New Frontier in Biology - PMC doi: 10.3390/biology10070570 Mechanobiology is the study of how biological components such as cells, tissues, and organs can sense and respond to mechanical cues to regulate numerous biological processes, including development, differentiation, physiology, and diseases . This Special Issue will help shed light on advances in biology through interdisciplinary integration of physics, chemistry, mathematics, and engineering, focusing on the state-of-the-art knowledge of mechanobiology and the application of mechanobiology principles. 4.Jansen K.A., Donato D.M., Balcioglu H.E., Schmidt T., Danen E.H., Koenderink G.H. A guide to mechanobiology: Where biology and physics meet. 11.Sun Y., Kim D.-H., Simmons C.A. Integrative Mechanobiology: Micro- and Nano-Techniques in Cell Mechanobiology.
[52] Cellular mechanotransduction in health and diseases: from molecular ... — Advertisement Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets Signal Transduction and Targeted Therapy volume 8, Article number: 282 (2023) Cite this article 5427 Accesses 6 Citations 5 Altmetric Metrics details Subjects Abstract Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical signals regarding cell activities and metabolism. Mechanotransduction has been expected to trigger multiple biological processes, such as embryonic development, tissue repair and regeneration. This review systematically summarizes the characteristics and regulatory mechanisms of typical mechanical cues in normal conditions and diseases with the updated evidence. We also reviewed the key signaling pathways, therapeutic targets and cutting-edge clinical applications of diseases related to mechanical cues.
[53] The Molecular Basis of Mechanosensory Transduction - PMC — Mechanotransduction occurs through specialized proteins that open an ion channel pore in response to a mechanical stimulus. In the nervous system, sensory transduction culminates in change of the electrical potential of a neuron This is accomplished by proteins in the membrane called ion channels, which are gated pores that allow the exchange of ions across the cell membrane. Although G-protein signaling is a commonly utilized mechanism for signal transduction, in mechanosensory systems, stimuli induce electrical activity by directly gating transduction channels. To begin the search for the underlying mechanotransduction channels, Lumpkin and colleagues investigated the gene expression profile of Merkel cells. NompC TRP channel required for vertebrate sensory hair cell mechanotransduction. Acid-sensing ion channels ASIC2 and ASIC3 do not contribute to mechanically activated currents in mammalian sensory neurones.
[55] Mechanotransduction: from the cell surface to the nucleus via RhoA ... — The RhoA signalling pathway is central to mechanotransduction because it plays a key role in regulating the actin cytoskeleton and its response to mechanical force . ... In preliminary experiments we have found that Rnd3 levels are depressed when normal and breast cancer epithelial cells are cultured on more rigid substrates (E Monaghan-Benson
[56] Theories and Milestones - Mechanobiology Institute, National University ... — RESEARCH @ MBI Michael Sheetz, Director of the Mechanobiology Institute, National University of Singapore and colleagues from Columbia University, New York, published a review in Nature Reviews Molecular Cell Biology that explores the history of mechanotransduction and considers the current models of With more and more researchers realizing the importance of how mechanical forces affect cell biology, mechanobiology is primed to expand in the near future, and to revolutionize our comprehension of cell growth, differentiation or apoptosis. Our research aims to interrogate biological systems from a physical and mechanical perspective at the molecular, cellular, and tissue level, with the eventual goal to leverage basic science discoveries in mechanobiology into biomedical innovations. © 2022 Mechanobiology Institute, National University of Singapore (MBI)
[59] Key developments that impacted the field of mechanobiology and ... — Advances in mechanobiology have evolved through insights from multiple disciplines including structural engineering, biomechanics, vascular biology, and orthopaedics. ... Here, we addressed a history of the field, but we limited our discussions to advances in musculoskeletal mechanobiology, primarily in bone, tendon, and ligament tissues
[60] PDF — For more information on Mechanobiology please visit MBinfo: www.mechanobio.info B teve olf n nre ong c Mechanobiology Institute, Singapore National University of Singapore T-Lab, #05-01, 5A Engineering Drive 1, S117411 The field of mechanobiology has grown dramatically in the past decade. With this growth came ground breaking experiments,
[89] Mechanobiology - Wikipedia — It focuses on how physical forces and changes in the mechanical properties of cells and tissues contribute to development, cell differentiation, physiology, and disease. The movement of joints, compressive loads on the cartilage and bone during exercise, and shear pressure on the blood vessel during blood circulation are all examples of mechanical forces in human tissues. A major challenge in the field is understanding mechanotransduction—the molecular mechanisms by which cells sense and respond to mechanical signals. While medicine has typically looked for the genetic and biochemical basis of disease, advances in mechanobiology suggest that changes in cell mechanics, extracellular matrix structure, or mechanotransduction may contribute to the development of many diseases, including atherosclerosis, fibrosis, asthma, osteoporosis, heart failure, and cancer.
[91] Advanced materials technologies to unravel mechanobiological phenomena — Advancements in materials-driven mechanobiology have yielded significant progress. Mechanobiology explores how cellular and tissue mechanics impact development, physiology, and disease, where extracellular matrix (ECM) dynamically interacts with cells. Biomaterial-based platforms emulate synthetic ECMs, offering precise control over cellular behaviors by adjusting mechanical properties. Recent
[92] Mechanobiology-informed biomaterial and tissue engineering strategies ... — It has flourished coinciding with the development and characterization of novel biomaterials and biomaterial construct fabrication methods; engineered biomaterial constructs act as extracellular microenvironments with well-controlled physical properties that allow tissue engineers to study the effects of these properties on the behaviors of
[93] Biomaterials-Based Strategies for the Engineering of Mechanically ... — The HGPs can be engineered to present therapeutic factors in a controlled fashion. 62, 63 Through the covalent linkage, the secondary network can exert mechanical constraints on the hydrogel particles, leading to the deformation of HGPs as evidenced by the diffuse interphase between individual HGPs and the secondary matrix in the cryogenic
[94] Mechanobiomaterials: Harnessing mechanobiology principles for tissue ... — When exogenous cells are incorporated into biomaterials for cell-based therapy, another basic consideration is the optimization of the mechanical environment of the cells to enable their ability to mediate tissue regeneration. Based on these two considerations, a typical workflow for the inverse design of mechanobiomaterials was proposed (Fig
[96] Translating Mechanobiology to the Clinic: A Panel Discussion from the ... — The goal of the panel was to initiate a dialogue and share pearls of wisdom from participants’ successes and failures in academia and in industry toward translating scientific discoveries in mechanobiology to technology products in the market or toward devices or drugs that impact clinical care. From the view of Dennis Discher, translational research is the process of taking new ideas developed in laboratory research and moving them to a broader community outside of the original laboratory, including other laboratories, companies, and the clinic.
[99] Mechanobiology of mesenchymal stem cells: Perspective into mechanical ... — Emerging research on stem cell mechanobiology has also been focused on dynamic mechanical loading, nonlinear strain-stiffening, ECM stiffness gradients, and soluble growth factors that can be trapped in ECM and released during controlled matrix degradation. ... Mechanically induced osteogenic differentiation - the role of RhoA, ROCKII and
[103] Cancer cell mechanobiology: a new frontier for cancer research — Cancer cell mechanobiology: a new frontier for cancer research - ScienceDirect Cancer cell mechanobiology: a new frontier for cancer research The study of physical and mechanical features of cancer cells, or cancer cell mechanobiology, is a new frontier in cancer research. Such studies may enhance our understanding of the disease process, especially mechanisms associated with cancer cell invasion and metastasis, and may help the effort of developing diagnostic biomarkers and therapeutic drug targets. Subsequent studies from us and others further demonstrated that cell mechanical properties are strongly associated with cancer cell invasive and metastatic potential, and thus may serve as a diagnostic marker of detecting cancer cells in human body fluid samples. For all open access content, the relevant licensing terms apply.
[104] How Mechanobiology is Enhancing Cancer Treatments — Herbert Levine says mechanobiology could hold key to helping immune therapy succeed in combating certain solid cancer tumors. “This is a physical phenomenon,” says Herbert Levine, Northeastern University distinguished professor of physics and bioengineering. The growing field of mechanobiology hopes to overcome treatment hurdles by partnering biologists with engineers and physicists who understand physical barriers and how they interact with cells, says Levine, who spoke at a two-day Global Summit on Mechanobiology and Mechanomedicine on Northeastern’s Boston campus. A biologist will try to figure out how cells encode the blueprint for treatment while the engineer wants to understand how the regrowth “physically works in the real world in real space,” he says.
[105] The emerging promise of tumour mechanobiology in cancer treatment — The mechanical properties of cancer cells and TME affect different features of tumours. ECM stiffness impacts on development, progression, and drug resistance of cancer cells. Modulating the mechanical properties of cancer cells can ameliorate treatment efficacy. The mechanical properties of cancer cells are determined by such a complex interconnectivity of events that Cancer Cell Cancer Cell Cancer Cell Functions and clinical significance of mechanical tumor microenvironment: cancer cell sensing, mechanobiology and metastasis Mechanical compression drives cancer cells toward invasive phenotype On the significance of the electrostatic differences between cancer and normal cells: Comment on: “Improving cancer treatments via dynamical biophysical models” by Kuznetsov et al.
[108] Unlocking crop potential—advancing plant phenomics for ... - Springer — The recent advancements in imaging techniques and high throughput platforms for real time measurement of crop traits under both controlled environments and open field conditions under heat stress have been described in "High throughput phenotyping and AI technologies for deciphering crop resilience to heat stress. The major developments in
[110] Opportunities and avenues for achieving crop climate resilience — The promise of achieving crop climate resilience. Advances in genomics have anchored sequencing, annotation and assemblage of several elite and progenitor crop species. GWAS methods can now help identify novel allelic variations for several climate-adaptive traits. Accumulated multi-omics data informs GAB (genomics-assisted breeding), whilst
[134] Cellular mechanotransduction in health and diseases: from molecular ... — Advertisement Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets Signal Transduction and Targeted Therapy volume 8, Article number: 282 (2023) Cite this article 5427 Accesses 6 Citations 5 Altmetric Metrics details Subjects Abstract Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical signals regarding cell activities and metabolism. Mechanotransduction has been expected to trigger multiple biological processes, such as embryonic development, tissue repair and regeneration. This review systematically summarizes the characteristics and regulatory mechanisms of typical mechanical cues in normal conditions and diseases with the updated evidence. We also reviewed the key signaling pathways, therapeutic targets and cutting-edge clinical applications of diseases related to mechanical cues.
[135] Recent advances in the treatment of osteoarthritis - PMC — Keywords: Osteoarthritis, OA phenotype, therapy, inflammation, subchondral bone, cartilage, pain, metabolic syndrome, senescence The results of a phase Ib study of i.a. injected sprifermin in patients with symptomatic knee OA found a statistically significant dose-dependent reduction in loss of total femorotibial cartilage thickness compared to placebo after 12 months of follow up 13. 10.1097/j.pain.0000000000001466 [DOI] [PubMed] [Google Scholar]; F1000 Recommendation 10.1097/j.pain.0000000000001625 [DOI] [PMC free article] [PubMed] [Google Scholar] : Tropomyosin-related kinase A (TrkA) inhibition for the treatment of painful knee osteoarthritis: results from a randomized controlled phase 2a trial. 10.1016/j.neuroscience.2015.03.042 [DOI] [PMC free article] [PubMed] [Google Scholar] 10.1097/j.pain.0000000000000986 [DOI] [PMC free article] [PubMed] [Google Scholar]; F1000 Recommendation 10.1016/j.semarthrit.2019.01.005 [DOI] [PMC free article] [PubMed] [Google Scholar] 10.1016/j.bone.2017.07.028 [DOI] [PMC free article] [PubMed] [Google Scholar]
[137] Biophysical and Biochemical Roles of Shear Stress on Endothelium: A ... — Hemodynamic shear stress, the frictional force exerted by blood flow on the endothelium, mediates vascular homeostasis. This review examines the biophysical nature and biochemical effects of shear stress on endothelial cells, with a particular focus on its impact on cardiovascular pathophysiology. Atherosclerosis develops preferentially at arterial branches and curvatures, where disturbed flow
[138] Mechanotransduction pathways in the regulation of cartilage chondrocyte ... — According to clinical and animal studies, excessive mechanical stress is instrumental in the initiation and development of osteoarthritis (OA) due to articular cartilage degradation (Figure 1). 5 , 6 FIGURE 1.
[139] Cardiovascular Drugs and Osteoarthritis: Effects of Targeting Ion ... — Osteoarthritis (OA) and cardiovascular diseases (CVD) share many similar features, including similar risk factors and molecular mechanisms. A great number of cardiovascular drugs act via different ion channels and change ion balance, thus modulating cell metabolism, osmotic responses, turnover of cartilage extracellular matrix and inflammation.
[140] Integrins In Mechanotransduction - PMC - PubMed Central (PMC) — Integrins play crucial roles, either as direct mechanotransducers, as transmitters of force to other elements, or as intermediates on pathways initiated by other receptors. In this review, we briefly summarize our current understanding of mechanotransduction, with emphasis on the role of integrins in these processes.
[142] Integrins in mechanotransduction - PubMed — Forces acting on cells govern many important regulatory events during development, normal physiology, and disease processes. Integrin-mediated adhesions, which transmit forces between the extracellular matrix and the actin cytoskeleton, play a central role in transducing effects of forces to regulat …
[145] Endothelial cytoskeleton in mechanotransduction and vascular ... - PubMed — This review focuses on the role of cytoskeletal components in membrane, cytoplasm, and nucleus in mechanotransduction, with an emphasis on their structure, mechanical and biological behaviors, dynamic interactions, and response to mechanical forces. The collaboration between membrane cytoskeleton, cytoplasmic cytoskeleton, and nucleoskeleton is
[148] Effects of shear stress on vascular endothelial functions in ... — ECs have the ability to actively sense, integrate, and convert mechanical stimuli by shear stress into biochemical signals that further induces intracellular changes (such as the opening and closing of ion channels, activation and transcription of signaling pathways).
[149] Shear stress-initiated signaling and its regulation of endothelial ... — The effects of fluid shear stress on endothelial gene expression and the ... This diagram illustrates that multiple signaling pathways coordinate to form mechanoresponsive networks to modulate EC phenotype and function. ... Li YS, Yuan S, Shyy JY, Chien S. Interplay between integrins and FLK-1 in shear stress-induced signaling. Am J Physiol
[150] Biophysical and Biochemical Roles of Shear Stress on Endothelium: A ... — The frictional force exerted by blood flow on the surface of endothelial cells (ECs) is known as hemodynamic shear stress. This force plays a pivotal role in maintaining endothelial homeostasis by influencing a range of cellular events, including proliferation, cell death, inflammatory responses, activation, and transdifferentiation. 1 In the late 15th century, Leonardo da Vinci first
[151] Mechanotransduction in tissue engineering: Insights into the ... — Mechanotransduction in tissue engineering: Insights into the interaction of stem cells with biomechanical cues - ScienceDirect In addition, this work provides an overview of advanced strategies using stem cells and biomaterial scaffolds that enable precise spatial and temporal control of mechanical signals and offer great potential for the fields of tissue engineering and regenerative medicine will be presented. In addition, this work examines how the development of biomaterials with specific mechanical properties affects stem cell behavior by mimicking the mechanical environment of different tissue types. By understanding the different types of mechanosensors and their functions, researchers can gain valuable insights into how cells respond to mechanical stimuli and develop more effective strategies for tissue engineering and regenerative medicine.
[159] Mechanotherapy: how physical therapists' prescription of exercise ... — Abstract Mechanotransduction is the physiological process where cells sense and respond to mechanical loads. This paper reclaims the term "mechanotherapy" and presents the current scientific knowledge underpinning how load may be used therapeutically to stimulate tissue repair and remodelling in tendon, muscle, cartilage and bone.
[161] Mechanotransduction in Musculoskeletal Tissue Regeneration: Effects of ... — The objective of this review is to develop a molecular understanding of the mechanotransduction processes in tissue regeneration, which may provide new insights into bone physiology.
[174] Mechanotransduction in Development - ScienceDirect — Recent experimental evidence demonstrates that mechanical cues generated by morphogenesis activate mechanotransduction pathways, which in turn regulate cytoskeleton remodeling, cell proliferation, tissue differentiation. Here, we review such processes of mechanotransduction involved in development, after a short description of the primary findings having first suggested mechanical factors to play a major role in proliferation, cytoskeleton reaction, or differentiation in cell culture, with the most recent findings in the underlying molecular mechanisms that translate mechanical signals into biochemical cues leading to the activation of transduction pathways. Mechanotransduction in embryogenesis was initially proposed to play a major role in active shape change responses of cells to mechanical stimulation by the morphogenetic movements of the environmental tissue.
[178] Harnessing Mechanobiology for Tissue Engineering - PubMed — A primary challenge in tissue engineering is to recapitulate both the structural and functional features of whole tissues and organs. In vivo, patterning of the body plan and constituent tissues emerges from the carefully orchestrated interactions between the transcriptional programs that give rise …
[179] 3D scaffolds-specific cellular mechanoresponse as a pivotal ... - Springer — In tissue engineering, the mechanical properties of the extracellular matrix (ECM) or scaffolds have increasingly been considered to impact therapeutic efficacy by regulating cell behaviors, including differentiation, proliferation, migration, and adhesion. However, the understanding of how cells sense, integrate, and convert the mechanical cues from the ECM cues into biochemical signals to
[181] Mechanotransduction in tissue engineering: Insights into the ... — Mechanotransduction in tissue engineering: Insights into the interaction of stem cells with biomechanical cues - ScienceDirect In addition, this work provides an overview of advanced strategies using stem cells and biomaterial scaffolds that enable precise spatial and temporal control of mechanical signals and offer great potential for the fields of tissue engineering and regenerative medicine will be presented. In addition, this work examines how the development of biomaterials with specific mechanical properties affects stem cell behavior by mimicking the mechanical environment of different tissue types. By understanding the different types of mechanosensors and their functions, researchers can gain valuable insights into how cells respond to mechanical stimuli and develop more effective strategies for tissue engineering and regenerative medicine.
[183] Mechanobiology in wound healing - ScienceDirect — Challenges lie ahead. For instance, the ECM can significantly contribute to cellular mechanics and wound healing through mechanisms such as activation of cell surface receptors and through long-range mechanical interactions (8). It is therefore desirable to culture cells on or in ECM mimics such as widely used biocompatible hydrogels before
[184] Mechanobiology of skin diseases and wound healing - ScienceDirect — Skin diseases and dysfunctional wound healing pose a significant health-care challenge (Fig. 1).For example, overhealing occurring in burns and trauma leads to severe functional disabilities costing the economy over $4 billion per year , , , .Keloids, which are characterized by excessive fibrosis in the areas of the skin with high strain , represent another major fibrotic
[186] Mechanoregulation of Wound Healing and Skin Homeostasis — Basic and clinical studies on mechanobiology of cells and tissues point to the importance of mechanical forces in the process of skin regeneration and wound healing. These studies result in the development of new therapies that use mechanical force
[187] Epithelial mechanobiology, skin wound healing, and the stem cell niche — Skin wound healing is a vital process that is important for re-establishing the epithelial barrier following disease or injury. Aberrant or delayed skin wound healing increases the risk of infection, causes patient morbidity, and may lead to the formation of scar tissue.
[189] Helical nanofiber yarn enabling highly stretchable engineered ... — Development of microtissues that possess mechanical properties mimicking those of native stretchable tissues, such as muscle and tendon, is in high demand for tissue engineering and regenerative medicine.
[192] Manufacturing of Anisotropic Protein-Based Scaffolds to Precisely Mimic ... — Biological and mechanical mismatches between engineered scaffolds and native tissues poses widespread challenges for tissue restoration. Native-like anisotropy is a critical characteristic for functional tissue replacements, yet it is an often-overlooked aspect when designing new scaffolds. In this study, fiber-reinforced tubular scaffolds are developed, mimicking the anisotropic
[224] Mechanobiology - an overview | ScienceDirect Topics — A more comprehensive and improved understanding of mechanobiology may greatly facilitate the development of new therapies that control mechanical forces and thereby specifically induce desired molecular, cellular, tissue, and/or organ formation, changes, or repair. Mechanobiology is a rapidly growing research area focused on how mechanical forces and properties influence biological systems at the cell, molecular, and tissue level, and how those biological systems, in turn, control mechanical parameters. A more comprehensive and improved understanding of mechanobiology may greatly facilitate the development of new therapies that act by controlling mechanical forces and thereby specifically induce desired molecular, cellular, tissue, and/or organ formation, changes, or repair.
[225] PDF — nisms that underlie these processes led to the emergence of the field of mechanobiology, which is an extremely interdisciplinary field of research at the interface between biology, physics, material science, and bioengineering. Researchers have been focusing on elucidating how cells sense and transduce me-
[236] Mechanobiomaterials: Harnessing mechanobiology principles for tissue ... — Mechanical stimuli are known to play critical roles in mediating tissue repair and regeneration. Recently, this knowledge has led to a paradigm shift toward proactive programming of biological functionalities of biomaterials by leveraging mechanics-geometry-biofunction relationships, which are beginning to shape the newly emerging field of mechanobiomaterials.
[237] Designer Biomaterials for Mechanobiology - PMC — Biomaterials engineered with specific bioactive ligands, tunable mechanical properties, and complex architectural features have emerged as powerful tools to probe how cells sense and respond to the physical properties of their material surroundings, and ultimately provide designer approaches to control cell function. (a) Schematic of a cell embedded in a fibrous-rich, mechanically anisotropic 3D microenvironment; (b) multiple designer parameters to orthogonally control specific properties of synthetic analogs of extracellular matrices, such as crosslinking density, matrix degradability, fiber architecture, and viscoelastic mechanics. In contrast to planar surfaces, embedded cells in soft matrices spread well and display a polarized morphology, but remained round in stiff hydrogels, suggesting that in addition to stiffness, matrix degradation – the breakage of crosslinks via passive hydrolysis or cell-mediated enzymatic cleavage – is a key component in regulating cell morphology in 3D microenvironment47,48.
[239] Mechanobiomaterials: A rising field using mechanobiology principles to ... — This field integrates biology, biomechanics, materials science, and bioengineering to create biomaterials that proactively influence cell and tissue responses through mechanical cues.
[240] Mechanobiomaterials: A rising field using mechanobiology principles to ... — To profile this emerging field, the authors elucidate the fundamental principles in modulating biological responses with material–tissue mechanical interactions, illustrate recent findings on the relationships between material properties and biological responses, discuss the importance of mathematical/physical models and numerical simulations in optimizing material properties and geometry, and outline design strategies for mechanobiomaterials and their potential for tissue repair and regeneration. This has led to advances in the design of biomaterials to regulate the responses of surrounding tissue and cells through mechanical interactions, resulting in enhanced tissue repair and regeneration. The authors summarize the fundamentals of material-tissue mechanical interactions, the relationship between material mechanics and biological responses, and the principles for designing mechanobiomaterials for tissue repair and regeneration.
[243] Mechanobiology: Shaping the future of cellular form and function — However, a true understanding of mechanobiology will require integration with gene theory and a parallel suite of technological breakthroughs in our ability to measure the mechanical properties and physical forces imposed upon and generated by living systems, ideally with high spatial and temporal resolution.
[244] Exploring the intersection of mechanobiology and artificial ... — In this regard, artificial intelligence approaches may enable several transformative advances in research, such as advanced data analysis (e.g. live-cell imaging, cellular pattern recognition), predictive modeling (e.g., mechanical properties of tissue and cells), automation of experimental procedures (e.g., atomic force microscopy, tweezers), integration of multi-scale data (from cells to tissues), or new insights into mechanotransduction pathways (e.g., gene networks, protein interactions, and cellular pathways). c Measurements of forces from different techniques, either at the multi-cell level (such as fluorescence and light microscopy or AFM curves) or at the bulk and single-cell level (such as DNA/RNA sequencing or genomic enrichment) are used as inputs for machine learning (ML) or artificial intelligence (AI)-based algorithms, which are then trained to provide outputs and predictions such as the cell and ECM mechanical properties, cell states and heterogeneity, or protein structure and gene expression.
[246] Mechanobiology in Soft Tissue Engineering - ScienceDirect — The prominent role of mechanobiology, in native tissue development and function, has given rise to various tissue engineering (TE) approaches that utilize bioreactors to apply dynamic mechanical stimulation, in an attempt to engineer functional soft tissue replacements, or disease state models. Current TE approaches are largely scaffold-based
[247] A novel bioreactor system for biaxial mechanical loading enhances the ... — Furthermore, the role of mechanical stimulation bioreactors can be broadened beyond the conventional approach of enhancing the quality of tissue-engineered cartilage constructs 19. ... In order to study the basic mechanobiology of chondrocytes in a physiologically relevant manner, bioreactors should be able to apply compression and shear
[248] A 3D printed mechanical bioreactor for investigating mechanobiology and ... — Introduction. Mechanobiology and tissue engineering approaches require a mechanical bioreactor system that can apply user-defined cyclic strains to cells and tissues in vitro and mechanically evaluate the developing tissues. The objective of this study was to design, build, and evaluate a low-cost, customizable, and multifunctional mechanical bioreactor system.
[251] Mechanobiomaterials: Harnessing mechanobiology principles for tissue ... — The major objective of mechanobiomaterials is to design biomaterials that can dynamically and consistently adapt and respond to the changing mechanical environment of tissues and cells to enhance their regenerative potential through appropriate mechanical stimuli. 9, 13 This is a fast-emerging field at the interface of biology, biomechanics
[252] Mechanobiomaterials: A rising field using mechanobiology principles to ... — To profile this emerging field, the authors elucidate the fundamental principles in modulating biological responses with material–tissue mechanical interactions, illustrate recent findings on the relationships between material properties and biological responses, discuss the importance of mathematical/physical models and numerical simulations in optimizing material properties and geometry, and outline design strategies for mechanobiomaterials and their potential for tissue repair and regeneration. This has led to advances in the design of biomaterials to regulate the responses of surrounding tissue and cells through mechanical interactions, resulting in enhanced tissue repair and regeneration. The authors summarize the fundamentals of material-tissue mechanical interactions, the relationship between material mechanics and biological responses, and the principles for designing mechanobiomaterials for tissue repair and regeneration.
[262] Mechanobiology - an overview | ScienceDirect Topics — A more comprehensive and improved understanding of mechanobiology may greatly facilitate the development of new therapies that control mechanical forces and thereby specifically induce desired molecular, cellular, tissue, and/or organ formation, changes, or repair. Mechanobiology is a rapidly growing research area focused on how mechanical forces and properties influence biological systems at the cell, molecular, and tissue level, and how those biological systems, in turn, control mechanical parameters. A more comprehensive and improved understanding of mechanobiology may greatly facilitate the development of new therapies that act by controlling mechanical forces and thereby specifically induce desired molecular, cellular, tissue, and/or organ formation, changes, or repair.
[263] Trends and Hotspots in Mechanobiology: A Bibliometric Analysis from ... — Additionally, through the construction of knowledge maps and collaboration networks, this study provides valuable insights for future academic developments. The analysis also identifies current research gaps and proposes potential directions for theoretical advancement and application expansion in mechanobiology.
[264] Mechanobiology: A New Frontier in Biology - PMC — Mechanobiology: A New Frontier in Biology - PMC doi: 10.3390/biology10070570 Mechanobiology is the study of how biological components such as cells, tissues, and organs can sense and respond to mechanical cues to regulate numerous biological processes, including development, differentiation, physiology, and diseases . This Special Issue will help shed light on advances in biology through interdisciplinary integration of physics, chemistry, mathematics, and engineering, focusing on the state-of-the-art knowledge of mechanobiology and the application of mechanobiology principles. 4.Jansen K.A., Donato D.M., Balcioglu H.E., Schmidt T., Danen E.H., Koenderink G.H. A guide to mechanobiology: Where biology and physics meet. 11.Sun Y., Kim D.-H., Simmons C.A. Integrative Mechanobiology: Micro- and Nano-Techniques in Cell Mechanobiology.
[265] Thinking multi-scale to advance mechanobiology - PMC — We are inviting submissions of articles on the role of mechanobiology in health and disease with the aim of publishing high quality research devoted to advance our understanding of mechanics shaping biological function. Although the biomechanical frontiers that cells face have perhaps always been most evident in the context of the physical behaviour of cells, advances in the past few years have demonstrated the impact of mechanical force on cellular function in many biological systems in health and disease. What all these examples have in common is the prospect of curing disease by tuning the control of mechanical force over biological function at multiple scales from molecules, to single cells, tissues and organs.
[266] Exploring the intersection of mechanobiology and artificial ... — In this regard, artificial intelligence approaches may enable several transformative advances in research, such as advanced data analysis (e.g. live-cell imaging, cellular pattern recognition), predictive modeling (e.g., mechanical properties of tissue and cells), automation of experimental procedures (e.g., atomic force microscopy, tweezers), integration of multi-scale data (from cells to tissues), or new insights into mechanotransduction pathways (e.g., gene networks, protein interactions, and cellular pathways). c Measurements of forces from different techniques, either at the multi-cell level (such as fluorescence and light microscopy or AFM curves) or at the bulk and single-cell level (such as DNA/RNA sequencing or genomic enrichment) are used as inputs for machine learning (ML) or artificial intelligence (AI)-based algorithms, which are then trained to provide outputs and predictions such as the cell and ECM mechanical properties, cell states and heterogeneity, or protein structure and gene expression.
[268] Unlocking Potential: The Intersection of Mechanobiology and ... - Archyde — (2024) developed “Machine learning interpretable models of cell mechanics from protein images,” indicating how AI can extract meaningful insights from complex biological data, possibly leading to new biomarkers and therapeutic targets related to ECM mechanics. As the inventors note it is, “an open machine learning based tool to interpret nano-indentation data of soft tissues and materials.” This AI can quickly and accurately interpret nano-indentation data,enabling researchers and clinicians to gain deeper insights into tissue behavior,potentially leading to earlier disease detection and more effective treatments for conditions like fibrosis or cancer. The ECM’s stiffness can effect cell shape (morphology) and function.Researchers are now using AI to analyze cell morphology and mechanosensing capabilities, uncovering potential targets for new cancer therapies.
[271] Combined mechanistic modeling and machine-learning approaches in ... — Combined mechanistic modeling and machine-learning approaches in systems biology – A systematic literature review - ScienceDirect Combined mechanistic modeling and machine-learning approaches in systems biology – A systematic literature review A review of the scientific papers concerned with a recent investigation topic of increasing interest, that is the combination of Mechanistic Modeling (MM) and Machine Learning (ML) methods applied to the field of systems biology. Mechanistic-based Model simulations (MM) are an effective approach commonly employed, for research and learning purposes, to better investigate and understand the inherent behavior of biological systems. What are the limitations of mechanistic mathematical models and machine learning techniques in systems biology?
[283] Mechanobiology-informed biomaterial and tissue engineering strategies ... — It is paramount to study this mechanobiology and account for these mechanics-mediated behaviors to develop next-generation tissue engineering therapies that synergistically combine physical and chemical signals to direct cell fate.
[284] Trends in mechanobiology guided tissue engineering and tools to study ... — Trends in mechanobiology guided tissue engineering and tools to study cell-substrate interactions: a brief review | Biomaterials Research | Full Text This review would provide insights to the researchers who work on exploiting various mechanical properties of substrates to control the cellular and tissue functions for tissue engineering and regenerative applications, and also will shed light on the advancements of various techniques that could be utilized to unravel the unknown in the field of cellular mechanobiology. Researchers also need various tools to visualize and quantify the responses of the cells and tissues after being stimulated with the mechanical forces. J Cell Sci. 2017;130(1):51–61.
[285] Harnessing mechanobiology for tissue engineering - PMC — As an alternative to deforming tissue constructs using mechanical approaches, synthetic materials have been engineered to deform in response to light, temperature, or electric or magnetic field, thus applying mechanical forces to adhered or embedded cells (Figure 1F) (Cezar et al., 2016; Chandorkar et al., 2019; Sutton et al., 2017). These engineered platforms provide better control of engaging specific integrin heterodimers and cadherin types with some demonstration of promoting specific cellular responses such as cell fate regulation (Clark et al., 2020; Cosgrove et al., 2016), proliferation (Gray et al., 2008), cell orientation (Gloerich et al., 2017), collective migration speed and persistence (Borghi et al., 2010), tissue development (Li et al., 2017b; Weber et al., 2007) and regeneration (Cheng and García, 2013; Clark et al., 2020; Zhu et al., 2017).
[286] Exploring the intersection of mechanobiology and artificial ... — In this regard, artificial intelligence approaches may enable several transformative advances in research, such as advanced data analysis (e.g. live-cell imaging, cellular pattern recognition), predictive modeling (e.g., mechanical properties of tissue and cells), automation of experimental procedures (e.g., atomic force microscopy, tweezers), integration of multi-scale data (from cells to tissues), or new insights into mechanotransduction pathways (e.g., gene networks, protein interactions, and cellular pathways). c Measurements of forces from different techniques, either at the multi-cell level (such as fluorescence and light microscopy or AFM curves) or at the bulk and single-cell level (such as DNA/RNA sequencing or genomic enrichment) are used as inputs for machine learning (ML) or artificial intelligence (AI)-based algorithms, which are then trained to provide outputs and predictions such as the cell and ECM mechanical properties, cell states and heterogeneity, or protein structure and gene expression.
[301] Mechanotransduction in fibrosis: Mechanisms and treatment targets — Therefore, pathological tissue remodeling and consequent fibrosis is tightly regulated by mechanical forces generated by cell-cell and cell-matrix interaction and intracellular cytoskeletal changes. Numerous studies have revealed the involvement of the lysyl oxidase enzyme family in mouse models of tissue fibrosis in organs such as the heart, liver, and lungs by facilitating collagen cross linking (Al-u’datt, Allen, & Nattel, 2019; Bellaye et al., 2018; Chen et al., 2020). Mechanotransduction involving biochemical and mechanical pathways regulates the cellular response to injury, repair and fibrosis. The complex mechanisms involve assembly/disassembly of cytoplasmic actin, regulation of YAP/TAZ and MRTF activity, alteration of nuclear envelope composition and nuclear pore size, and modulation of EMT and EndoMT process, all of which could change the transcriptional activity and chromatin accessibility of genes related to fibrosis and tissue repair.
[302] Beyond matrix stiffness: targeting force-induced cancer ... - Cell Press — During tumor progression, mechanical abnormalities in the tumor microenvironment (TME) trigger signaling pathways in cells that activate cellular programs, resulting in tumor growth and drug resistance. In this review, we describe mechanisms of action for anti-cancer therapies and mechanotransduction programs that regulate cellular processes, including cell proliferation, apoptosis, survival
[303] Mechanotransduction in cancer - PMC - PubMed Central (PMC) — Within the past decade, and particularly in the last few years, there is increasing evidence that the stiffness of the extracellular matrix modulates cancer and stromal cell mechanics and function, influencing such disease hallmarks as angiogenesis, migration, and metastasis. This review briefly summarizes recent studies that investigate how cancer cells and fibrosis-relevant stromal cells respond to ECM stiffness, the possible sensing appendages and signaling mechanisms involved, and the emergence of novel substrates — including substrates with scar-like fractal heterogeneity — that mimic the in vivo mechanical environment of the cancer cell. This review summarizes some recent studies that use materials of tunable rigidity to identify the mechanosensing ability of cancer cells, how substrate stiffness affects some of the cancer hallmarks, and the possible mechanisms involved. doi: 10.1016/j.cell.2009.10.027.
[304] Mechano-therapeutics: Targeting Mechanical Signaling in Fibrosis and ... — The molecular determinants of myofibroblast activation in fibrosis and tumor stroma have traditionally been viewed to include biochemical agents, such as dysregulated growth factor and cytokine signaling, which profoundly alter the biology of fibroblasts, ultimately leading to overexuberant matrix deposition and fibrosis. In this Review, we will discuss pathological mechanisms driving tissue fibrogenesis with an emphasis on the role of the physical microenvironment (e.g. matrix stiffness) in the amplified activation of fibrogenic myofibroblasts during the development and progression of fibrotic diseases and desmoplastic tumors. While biochemical factors are undoubtedly involved in the activation of fibroblasts and development of fibrosis, a growing body of studies have reported that altered mechanical properties of the ECM (e.g. increased matrix stiffness) are major drivers of tissue fibrogenesis (Figure 1) (Santos & Lagares, 2018; Tschumperlin, Liu, & Tager, 2013).