UBC Math Bio Seminar: Magdalena Stolarska (Online)

It has been well established that the mechanical stiffness of the substrate with which cells interact affects various intracellular processes, including cell spread areas, speeds at which motile cells translocate, and the number and strength of cell-substrate adhesions. This mechanosensitivity is modulated through conformational changes in cell-substrate adhesion proteins that in turn regulate downstream processes, including processes involving proteins required for motility, actin and myosin. The aim of this work is to better understand how substrate stiffness affects actin dynamics and myosin activity in cell spreading. We present an axisymmetric model of a flat cell spreading on a two-dimensional substrate. The actin network is modeled as a viscous gel, and actin spreading and contraction dynamics are incorporated into the model as a local active rate of deformation. The model also incorporates membrane tension and stress-dependent focal adhesion dynamics, which in turn modulate a cell’s protrusive activity and speed of actin retrograde flow, thereby controlling the spreading rate. Using this model, we are able to recapitulate the three phases of cell spreading dynamics described in Gianonne et al. (Cell, 2004), and we predict how the balance of protrusive activity, actin retrograde flow, adhesion strength, and local actomyosin contractions are affected by substrate stiffness.