A multi-scale clutch model for adhesion complex mechanics

Abstract

Cell-matrix adhesion is a central mechanical function to a large number of phenomena in physiology and disease, including morphogenesis, wound healing and tumor cell invasion. Today, how single cells responds to different extracellular cues has been comprehensibly studied. However, how the mechanical behavior of the main individual molecules that form an adhesion complex cooperatively respond to force within the adhesion complex has not been addressed. This is a key aspect in cell adhesion because how these cell adhesion molecules respond to force determines not only cell-matrix behavior but, ultimately, cell function. To answer this question, we develop a multi-scale computational model for adhesion complexes mechanics. Based on the classical clutch hypothesis, we model individual adhesion chains made of a contractile actin network, a talin rod and an integrin molecule that binds at individual adhesion sites on the extracellular matrix. We explore several scenarios of integrins dynamics and analyze the effects of diverse extracellular matrices on the behavior of the adhesion molecules and on the whole adhesion complex. Our results explains how every single component of the adhesion chain mechanically responds to the contractile actomyosin force and show how they control the tractions forces exerted by the cell on the extracellular space. Importantly, our computational results are in agreement with previous experimental data both at the molecular and cell level. Our multi-scale clutch model presents a step forward not only to further understand adhesion complexes mechanics but also to, e.g., engineer better biomimetic materials, repair biological tissues or arrest invasive tumor migration. Author summaryCell-matrix adhesions are directly implicated in key biological processes such as tissue development, regeneration and tumor cell invasion. These cell functions are determined by how adhesion complexes feel and respond to mechanical forces. Still, how forces are transmitted through the individual cell adhesion molecules that integrate the adhesion complex is poorly understood. To address this issue, we develop a multi-scale clutch model for adhesion complexes where individual adhesion chains, made of integrin and talin molecules, are considered within classical clutch models. This approach provides a rich mechanosensivity insight of how the mechanics of cell adhesion works. It allows to integrate accurate biophysical models of individual adhesion molecules into whole adhesion complex models. Our multi-scale clutch approach allows to extend our current knowledge of adhesion complexes for physiology and disease, e.g., the regeneration of biological tissues or arrest invasive tumor migration, and for engineering better biomimetic materials.