Biomechanical model of cells probing the myosin-II-independent mechanosensing mechanism

Mechanosensing of cells to extracellular matrix (ECM) is highly active and plays a crucial role in various physiological processes. Growing numbers of studies provide evidence that cell sensitivity to ECM stiffness is a complex stress-strain feedback process. However, the mechanisms that rule this process are still not fully known. Here, an alternative mechanosensing scheme of cells, which is different from the previous myosin-II-based mechanisms, is proposed by employing the tension in cortical cytoskeletons (CSKs) as a force module to probe the substrate. The molecular mechanotransduction from cortical CSKs, through actin filaments and focal adhesions, and finally to the substrate, is mechanically modeled to scale the dynamic traction forces of cells. The developed model captures the characteristic spread of cells with respect to ECM stiffness whereby the spread is fully developed on a stiff substrate but not on a soft one. Furthermore, durotactic migration of cells on an elastic-gradient substrate is successfully modeled by the current method. The cells are concluded to migrate, actuated by the polarized traction forces from the stiffness gradient of the substrate and the stiffness matching between cells and substrate. Finally, the cells are proposed to actively target the preferred substrate by following a rule of mechanical matching between cells and substrate. This study provides a theoretical tool to advance our knowledge regarding the passive mechanical properties and the active sensing of cells, and further promotes the discovery of mechanosensing mechanisms as well as the material design for embryonic development and tissue homeostasis.