Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.06.23.546346v1?rss=1

Authors: Neelakshi, K., Caruso, A. P., Prokopiou, N., Logue, J. S.

Abstract:
Migrating cells must adapt to the mechanochemical properties of the microenvironment. Here, we demonstrate that intracellular [Ca2+] in melanoma cells rises in response to 2D confinement. Upon chelating Ca2+ or inhibiting Piezo1, cells were less likely to phenotypically transition from mesenchymal to fast amoeboid migration. In VCAM-1 coated microchannels, melanoma cells adopt a hybrid mode of migration, which has hallmarks of mesenchymal and amoeboid migration. In the absence of Piezo1 activity, cells predominantly adopted a mesenchymal mode of migration. In undulating channels, however, melanoma cells are almost entirely amoeboid. In agreement with a curvature induced increase in plasma membrane tension, this effect could be blocked by inhibiting Piezo1 or chelating Ca2+. In addition to ROCK2, we found that activation of inverted formin-2 (INF2) downstream of Piezo1/Ca2+ to be required for amoeboid migration. Thus, the activation of INF2 by Piezo1/Ca2+ constitutes an essential mechanism by which cells respond to confining environments.

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