Stiffness and Load-Dependent Spreading of Cell-Surface Adhesions are Emergent Properties of a Molecular Model

Abstract

Cells plated on a 2-D substrate form adhesions with that surface. These adhesions, consisting of aggregates of various proteins, including integrins, paxillin, vinculin, talin and others, are thought to be important in mechanosensation, the process by which the cell senses and adapts to mechanical properties of the surface, such as stiffness. At a molecular level, integrins in the adhesion bind to the extracellular matrix, while the various other proteins are involved in, among other things, binding to actin filaments that, in turn, apply a load to the adhesion. Several of these proteins (e.g. talin) undergo load-dependent state transitions that are thought to be important in both the load-dependent and the surface stiffness-dependent stability of the adhesions. Based on these molecular-level observations, we consider a grossly simplified version of an adhesion, made up of “molecules” that can bind to the surface in a strain-dependent manner and can undergo a load-dependent state transition. Remarkably, we find that, in Monte-Carlo simulations of these molecules, molecular aggregates are formed in a load- and stiffness-dependent fashion that closely mimics that seen in experiment. Furthermore, we find that these adhesions exhibit three phases of growth: 1) nucleation, where small, transient molecular aggregates form; 2) maturation, where adhesions grow quadratically in time; and 3) decay, where a short steady-state is followed by adhesion disassembly. These three phases of adhesion growth are also experimentally observed. These various properties of the Monte-Carlo simulation may be simply understood by analytic calculations. We therefore conclude that many experimental observations of stiffness- and load-dependent adhesion growth are emergent properties of molecular-mechanical systems with strain-dependent surface binding and a load-dependent state transition.