The nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments

Citations Over TimeTop 10% of 2021 papers

Abstract

Cell migration in confining microenvironments is limited by the ability of the stiff nucleus to deform through pores when migration paths are preexisting and elastic, but how cells generate these paths remains unclear. Here, we reveal a mechanism by which the nucleus mechanically generates migration paths for mesenchymal stem cells (MSCs) in confining microenvironments. MSCs migrate robustly in nanoporous, confining hydrogels that are viscoelastic and plastic but not in hydrogels that are more elastic. To migrate, MSCs first extend thin protrusions that widen over time because of a nuclear piston, thus opening up a migration path in a confining matrix. Theoretical modeling and experiments indicate that the nucleus pushing into the protrusion activates mechanosensitive ion channels, leading to an influx of ions that increases osmotic pressure, which outcompetes hydrostatic pressure to drive protrusion expansion. Thus, instead of limiting migration, the nucleus powers migration by generating migration paths.

Related Papers

• → Mechanosensitive ion channels in cell migration(2021)76 cited
• → Physiological and Pathological Functions of Mechanosensitive Ion Channels(2014)65 cited
• → Ion Channels with Mechanosensitivity in the Nervous System(2008)4 cited
• → Cardiovascular mechanosensitive ion channels—Translating physical forces into physiological responses(2021)5 cited
• → Reprint of: Mechanosensitive ion channels in cell migration(2021)4 cited