The bioenergetics of integrin-based adhesion, from single molecule dynamics to stability of macromolecular complexes

The forces actively generated by motile cells must be transmitted to their environment in a spatiotemporally regulated manner, in order to produce directional cellular motion. This task is accomplished through integrin-based adhesions, large macromolecular complexes that link the actin-cytoskelton inside the cell to its external environment. Despite their relatively large size, adhesions exhibit rapid dynamics, switching between assembly and disassembly in response to chemical and mechanical cues exerted by cytoplasmic biochemical signals, and intracellular/extracellular forces, respectively. While in material science, force typically disrupts adhesive contact, in this biological system, force has a more nuanced effect, capable of causing assembly or disassembly. This initially puzzled experimentalists and theorists alike, but investigation into the mechanisms regulating adhesion dynamics have progressively elucidated the origin of these phenomena. This review provides an overview of recent studies focused on the theoretical understanding of adhesion assembly and disassembly as well as the experimental studies that motivated them. We first concentrate on the kinetics of integrin receptors, which exhibit a complex response to force, and then investigate how this response manifests itself in macromolecular adhesion complexes. We then turn our attention to studies of adhesion plaque dynamics that link integrins to the actin-cytoskeleton, and explain how force can influence the assembly/disassembly of these macromolecular structure. Subsequently, we analyze the effect of force on integrins populations across lengthscales larger than single adhesions. Finally, we cover some theoretical studies that have considered both integrins and the adhesion plaque and discuss some potential future avenues of research.