A multiscale whole-cell theory for cell migration under geometric confinement

Cells actively sense and respond to the mechanical and geometric properties of the extracellular matrix (ECM). To explain the experimental observations of the regulatory roles of the ECM mechanics and geometry in mesenchymal migration, we have developed a multiscale whole-cell theory that considers the sensing of the constricted ECM domains. Our theory quantitatively captures the experimental dependence of the cell shape and migration speed on ECM viscoelasticity and confinement geometry. Importantly, we find that the cell migration speed and the channel width are inversely proportional. Our results further indicate the effect of curved channel geometries on cell spreading, morphology, and migration speed. Altogether, our theory not only captures the mesenchymal migration dynamics under confinement but also provides experimentally testable predictions for cell migration in complex tissue microenvironments.