Mechanosensitivity Occurs along the Adhesome's Force Train and Affects Traction Stress

Herein, we consider the process of force development along the adhesome within cell focal adhesions. Our model adhesome consists of the actin cytoskeleton-vinculin-talin-integrin-ligand-extracellular matrix-substrate force train. We specifically consider the effects of substrate stiffness on the force levels expected along the train and on the traction stresses they create at the substrate. We find that significant effects of substrate stiffness are manifest within each constitutive component of the force train and on the density and distribution of integrin/ligand anchorage points with the substrate. By following each component of the force train, we are able to delineate specific gaps in the quantitative descriptions of bond survival that must be addressed so that improved quantitative forecasts become possible. Our analysis provides, however, a rational description for the various levels of traction stresses that have been reported and of the effect of substrate stiffness. Our approach has the advantage of being quite clear as to how each constituent contributes to the net development of force and traction stress. We demonstrate that to provide truly quantitative forecasts for traction stress, a far more detailed description of integrin/ligand density and distribution is required. Although integrin density is already a well-recognized important feature of adhesion, our analysis places a finer point on it in the manner of how we evaluate the magnitude of traction stress. We provide mechanistic insight into how understanding of this vital element of the adhesion process may proceed by addressing mechanistic causes of integrin clustering that may lead to patterning.