The biophysics of cell motility through mechanochemically challenging environments.

Challenging mechanochemical environments (i.e., with varied mechanical and adhesive properties) are now known to induce a wide range of adaptive phenomena in motile cells. For instance, confinement and low adhesion may trigger a phenotypic transition to fast amoeboid (leader bleb-based) migration. The molecular mechanisms that underly these phenomena are beginning to be understood. Due to its size, the mechanical properties of the nucleus have been shown to limit and facilitate cell migration. Additionally, the activity of various transient receptor potential (TRP) channels is now known to be integral to cell migration in response to a multitude of biophysical stimuli. How cells integrate signals from the nucleus and plasma membrane, however, is unclear. The development of therapeutics that suppress cancer or enhance immune cell migration for immuno-oncology applications, etc., will require additional work to completely understand the molecular mechanisms that enable cells to navigate mechanochemically challenging environments.