Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels

TLDR

The study aimed to investigate how cells sense and adapt to mechanical stress by applying tensional forces to magnetic microbeads bound to integrin receptors and measuring bead displacement with sub‑micrometer optical microscopy. The authors used magnetic microbeads attached to integrin receptors, applied controlled tensional forces, and tracked bead displacement with sub‑micrometer resolution to probe cellular mechanotransduction. Cells exhibited four distinct mechanical responses—an immediate viscoelastic reaction, early adaptive attenuation, later stiffening under sustained stress, and a large‑scale repositioning under prolonged stress—each modulated by cytoskeletal tension, Rho signaling, mechanosensitive ion channels, Src kinases, and temperature, demonstrating multiple mechanisms for sensing and adapting to mechanical stress.

Abstract

To understand how cells sense and adapt to mechanical stress, we applied tensional forces to magnetic microbeads bound to cell-surface integrin receptors and measured changes in bead displacement with sub-micrometer resolution using optical microscopy. Cells exhibited four types of mechanical responses: (1) an immediate viscoelastic response; (2) early adaptive behavior characterized by pulse-to-pulse attenuation in response to oscillatory forces; (3) later adaptive cell stiffening with sustained (>15 second) static stresses; and (4) a large-scale repositioning response with prolonged (>1 minute) stress. Importantly, these adaptation responses differed biochemically. The immediate and early responses were affected by chemically dissipating cytoskeletal prestress (isometric tension), whereas the later adaptive response was not. The repositioning response was prevented by inhibiting tension through interference with Rho signaling, similar to the case of the immediate and early responses, but it was also prevented by blocking mechanosensitive ion channels or by inhibiting Src tyrosine kinases. All adaptive responses were suppressed by cooling cells to 4 degrees C to slow biochemical remodeling. Thus, cells use multiple mechanisms to sense and respond to static and dynamic changes in the level of mechanical stress applied to integrins.