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Mechanotransduction research focuses on understanding how cells sense and respond to mechanical stimuli by converting mechanical signals into biochemical and biological responses. Cells have been shown to respond to mechanical stimuli through specialized biological machinery such as adhesion complexes. Research in the last two decades helped in identifying key components of cellular mechanotransduction. In recent years, integrated approaches, which are highlighted here, are emerging to provide new insights into the mechanistic and theoretical underpinnings of mechanotransduction. In particular, mathematical modeling has helped elucidate the mechanism underlining ligand spacing and distribution sensing, as well as sensing viscoelastic properties of the extracellular matrix. In addition, molecular tension sensors have helped dissect the forces involved in mechanotransduction at high spatial and temporal resolutions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Cell migration and traction are essential to many biological phenomena, and one of their key features is sensitivity to substrate stiffness, which biophysical models, such as the motor-clutch model and the cell migration simulator can predict and explain. However, these models have not accounted for the finite size of adhesions, the spatial distribution of forces within adhesions. Here, we derive an expression that relates varying adhesion radius ( R) and spatial distribution of force within an adhesion (described by s) to the effective substrate stiffness ( κ sub ), as a function of the Young's modulus of the substrate ( E Y ), which yields the relation, κ sub = R s E Y , for two-dimensional cell cultures. Experimentally, we found that a cone-shaped force distribution ( s = 1.05) can describe the observed displacements of hydrogels deformed by adherent U251 glioma cells. Also, we found that the experimentally observed adhesion radius increases linearly with the cell protrusion force, consistent with the predictions of the motor-clutch model with spatially distributed clutches. We also found that, theoretically, the influence of one protrusion on another through a continuous elastic environment is negligible. Overall, we conclude cells can potentially control their own interpretation of the mechanics of the environment by controlling adhesion size and spatial distribution of forces within an adhesion., (© 2019 Wiley Periodicals, Inc.)