Force-dependent activation of actin elongation factor mDia1 protects the cytoskeleton from mechanical damage and facilitates stress fiber repair

Sergey V. Plotnikov and Fernando Valencia
Department of Cells and Systems Biology, University of Toronto
Friday, March 19, 2021 - 11:00am
https://utoronto.zoom.us/j/94049486250
Departmental Seminar
Abstract: 
Cells are truly the ultimate “smart-material” fine-tuning their mechanical properties to match the mechanical demands of their environments. Such plasticity of cell mechanics, which relies heavily on the spatiotemporal regulation of the actomyosin cytoskeleton, allows cells to migrate through narrow spaces, resist shear forces, and safeguard against mechanical damage. Yet, mechanisms of the adaptive changes in cell mechanics remain elusive. In this presentation, we will report a new mechanism whereby mechanically activated actin elongation factor mDia1 controls the dynamics of actin polymerization at focal adhesions, force bearing linkages between the actin cytoskeleton and extracellular matrix. By combining live-cell imaging with mathematical modelling, we show that actin polymerization at focal adhesions exhibits pulsatile dynamics where the spikes of mDia1 activity are triggered by cell-generated contractile forces. We show that suppression of mDia1-mediated actin polymerization at focal adhesions results in two-fold increase in mechanical tension on the stress fibers. This elevated tension correlates with an increased frequency of spontaneous stress fiber damage and decreased efficiency of zyxin-mediated stress fiber repair. Finally, we show that stress fiber protection by mDia1 is essential for differentiation of myofibroblasts, a highly contractile cells that are vital for wound healing. We conclude that tension-controlled actin polymerization at focal adhesions acts as a safety valve dampening excessive mechanical tension on the actin cytoskeleton and safeguarding stress fibers against mechanical damage.
Host: 
Sergey V. Plotnikov
Dept of Cell and Systems Biology