Physical influences of the extracellular environment on cell migration

Key Points Cells alter their migratory phenotypes and velocity in response to the physical properties of their extracellular environment. Confinement, adhesion, stiffness and topology of the extracellular environment are key physical variables influencing cell migration. Univariate profiles and phase diagrams enable an understanding of how physical variables influence cell migration. Numerical simulations enable systematic exploration of the phase space to highlight regions for experimental exploration. The physical properties of the extracellular environment — in terms of confinement, rigidity, surface topology and adhesion-ligand density — can have profound effects on the migration strategy and migration velocity of cells in different in vivo contexts. The way in which a cell migrates is influenced by the physical properties of its surroundings, in particular the properties of the extracellular matrix. How the physical aspects of the cell's environment affect cell migration poses a considerable challenge when trying to understand migration in complex tissue environments and hinders the extrapolation of in vitro analyses to in vivo situations. A comprehensive understanding of these problems requires an integrated biochemical and biophysical approach. In this Review, we outline the findings that have emerged from approaches that span these disciplines, with a focus on actin-based cell migration in environments with different stiffness, dimensionality and geometry.