Computational model of integrin adhesion elongation under an actin fiber

Cells create physical connections with the extracellular environment through adhesions. Nascent adhesions form at the leading edge of migrating cells and either undergo cycles of disassembly and reassembly, or elongate and stabilize at the end of actin fibers. How adhesions assemble has been addressed in several studies, but the exact role of actin fibers in the elongation and stabilization of nascent adhesions remains largely elusive. To address this question, here we extended our computational model of adhesion assembly by incorporating an actin fiber that locally promotes integrin activation. The model revealed that an actin fiber promotes adhesion stabilization and elongation. Actomyosin contractility from the fiber also promotes adhesion stabilization and elongation, by strengthening integrin-ligand interactions, but only up to a force threshold. Above this force threshold, most integrin-ligand bonds fail, and the adhesion disassembles. In the absence of contraction, actin fibers still support adhesions stabilization. Collectively, our results provide a picture in which myosin activity is dispensable for adhesion stabilization and elongation under an actin fiber, offering a framework for interpreting several previous experimental observations. Author summaryThe formation of cell adhesions is important for numerous biological processes, including cell migration, differentiation, survival, tissue morphogenesis, and wound healing. However, to fully understand how adhesions control biological processes, we need to unravel the biophysical principles underlying their assembly and maintenance. Experimentally, assessing how adhesion proteins form and maintain adhesions is difficult. The mechanisms by which adhesion proteins regulate adhesions are not well understood, and controversy exists on the roll of cell contractility. Here, we developed a model of adhesion assembly and characterized how adhesions elongate in the presence and absence of contraction. We found that force is not needed for the transition of adhesions into elongated morphologies.

Automated summary

Cells create physical connections with the extracellular environment through adhesions. Nascent adhesions form at the leading edge of migrating cells and either undergo cycles of disassembly and reassembly, or elongate and stabilize at the end of actin fibers. The exact role of actin fibers in the elongation and stabilization of nascent adhesions remains largely elusive.