Extracellular Hydraulic Resistance Enhances Cell Migration
Cells migrating in vivo can encounter microenvironments with varying physical properties. One such physical variable is the viscosity of the fluid surrounding the cell. Increased fluid viscosity is expected to increase the hydraulic resistance experienced by the migrating cell and therefore decrease the cell speed. We demonstrate that contrary to this expected result, cells migrate faster in high viscosity media on 2D substrates. To reveal the molecular mechanism, we examined both actin
... both actin dynamics and water dynamics driven by ion channel activity. Results show that cells increased in area in high viscosity and actomyosin dynamics remained similar, except that actin retrograde flow speed is reduced. Inhibiting ion channel fluxes in high viscosity media results in a large reduction in cell speed, suggesting that water flux contributes to the observed speed increase. Moreover, inhibiting actin-dependent vesicular trafficking that transports ion channels from the ER to the cell boundary changes ion channel spatial positioning and reduces cell speed in high viscosity media. Cells also displayed altered Ca2+-activity in high viscosity media, and when cytoplasmic Ca2+ is sequestered, cell speed reduction and altered ion channel positioning were observed. Taken together, we find that the cell cytoplasmic actin-phase and water-phase are coupled during cell migration in high viscosity media. Directional water fluxes are mediated by ion channels whose position depend on actin-based vesicular trafficking. There are no significant changes in ion channel total content in high viscosity, in agreement with physical modeling that also predicts the observed cell speedup in high viscosity environment.