Comparative End-to-End Analysis of Ca²⁺-Signaling-Based Molecular Communication in Biological Tissues

Abstract

Calcium (Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> )-signaling-based molecular communication is a short-range communication process that diffuses and propagates ions between the cells of a tissue. The communication process is initiated via stimulation and amplification of the production of Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> ions within a cell; these ions then diffuse through a physical connection between cells called a gap junction. Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> signaling can be found in different classes of cell. In excitable cells, initiation of the Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> -signaling process is accompanied by an electrical component; for nonexcitable cell types, the electrical component is absent; while hybrid cells exhibit both behaviors. This paper provides a comparison and analysis of the communication behavior in tissues comprised three specific cell types that utilize Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> signaling: epithelium cells (nonexcitable), smooth muscle cells (excitable), and astrocytes (hybrid). The analysis focuses on spatiotemporal Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> concentration dynamics and how they are influenced by the intracellular signaling process, the molecular diffusion delay, the gain and capacity of the communication channel, as well as intracellular signaling interference. This analysis of the communication behavior in the context of tissues provides insights useful for, inter alia, the design of nanomachines that are situated within tissues and that use analysis of the communication channel to infer tissue health.