Cooperation of dual modes of cell motility promotes epithelial stress relaxation to accelerate wound healing.

Michael F Staddon,Visar Ajeti,Shiladitya Banerjee,A Pasha Tabatabai,Michael P Murrell,Dapeng Bi,Anand R Asthagiri

doi:10.1371/journal.pcbi.1006502

Abstract

Collective cell migration in cohesive units is vital for tissue morphogenesis, wound repair, and immune response. While the fundamental driving forces for collective cell motion stem from contractile and protrusive activities of individual cells, it remains unknown how their balance is optimized to maintain tissue cohesiveness and the fluidity for motion. Here we present a cell-based computational model for collective cell migration during wound healing that incorporates mechanochemical coupling of cell motion and adhesion kinetics with stochastic transformation of active motility forces. We show that a balance of protrusive motility and actomyosin contractility is optimized for accelerating the rate of wound repair, which is robust to variations in cell and substrate mechanical properties. This balance underlies rapid collective cell motion during wound healing, resulting from a tradeoff between tension mediated collective cell guidance and active stress relaxation in the tissue.

Highlights

Collective cell migration is central to tissue morphogenesis, wound repair and cancer metastasis [1]
Progress has been limited by the lack of an integrative framework that couples cellular physical behavior with stochastic biochemical dynamics underlying cell motion and adhesion
We ask: How do migrating cells sense changes in their physical environment? How do cells regulate their modes of motilities to optimize the speed of collective motion? What roles do tissue mechanical properties play in stress propagation and relaxation during wound repair? In particular, we find that an optimum mixture of protrusive and contractile cell activities at the wound edge accelerates the rate of wound healing under diverse conditions

Summary

Introduction

Collective cell migration is central to tissue morphogenesis, wound repair and cancer metastasis [1]. During tissue repair after wounding [2], or during closure of epithelial gaps [3, 4], collective cell migration enables the regeneration of a functional tissue. Gap closure is usually mediated by two distinct mechanisms for collective cell movement [5,6,7]. Cells around the gap can collectively assemble a supracellular actomyosin cable, known as a purse-string, which closes tissue voids via active contractile forces [6, 9]. It remains poorly understood how these two modes of collective cell movement, driven by the assembly of distinct actin network architectures, are regulated in diverse biophysical conditions

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