Influence of Curvature on Cell Motility and Morphology during Cancer Migration in Confined Microchannels

Microchannels often serve as highways for cancer migration, and their topology largely determines the migration efficiency. Curvature, a topological parameter in biological systems, has recently been reported to be efficient in guiding cell polarization and migration. Curvature varies widely along curved microchannels, while its influence on cell migration remains elusive. Here, we recapitulated the curved microchannels, as observed in clinical tumor tissues with hydrogels, and studied how cancer cells respond to curvature. We found that cells bend more significantly in a larger curvature and exhibit less spreading as well as lower motility. The underlying mechanism is probably based on the hindrance of the movement of cytoskeletal molecules at the curved microchannel walls. Collectively, our results demonstrated that the accelerated actin retrograde flow rate under local curvature has an effective negative regulation on cell motility and morphology, leading to shortened and bent cell morphologies as well as hampered cell migration efficiency.