Substratum stiffness tunes membrane voltage in mammary epithelial cells.

TitleSubstratum stiffness tunes membrane voltage in mammary epithelial cells.
Publication TypeJournal Article
Year of Publication2021
AuthorsSilver, BB, Zhang, SX, Rabie, EM, Nelson, CM
JournalJ Cell Sci
Volume134
Issue13
Date Published2021 Jul 01
ISSN1477-9137
Abstract

<p>Membrane voltage (Vm) plays a critical role in the regulation of several cellular behaviors, including proliferation, apoptosis and phenotypic plasticity. Many of these behaviors are affected by the stiffness of the underlying extracellular matrix, but the connections between Vm and the mechanical properties of the microenvironment are unclear. Here, we investigated the relationship between matrix stiffness and Vm by culturing mammary epithelial cells on synthetic substrata, the stiffnesses of which mimicked those of the normal mammary gland and breast tumors. Although proliferation is associated with depolarization, we surprisingly observed that cells are hyperpolarized when cultured on stiff substrata, a microenvironmental condition that enhances proliferation. Accordingly, we found that Vm becomes depolarized as stiffness decreases, in a manner dependent on intracellular Ca2+. Furthermore, inhibiting Ca2+-gated Cl- currents attenuates the effects of substratum stiffness on Vm. Specifically, we uncovered a role for cystic fibrosis transmembrane conductance regulator (CFTR) in the regulation of Vm by substratum stiffness. Taken together, these results suggest a novel role for CFTR and membrane voltage in the response of mammary epithelial cells to their mechanical microenvironment.</p>

DOI10.1242/jcs.256313
Alternate JournalJ Cell Sci
PubMed ID34114636
PubMed Central IDPMC8310660
Grant ListU01 CA214292 / CA / NCI NIH HHS / United States
GM134602 / / National Science Foundation /
R01 CA187692 / CA / NCI NIH HHS / United States
F30 GM134602 / GM / NIGMS NIH HHS / United States
CA187692 / NH / NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States