Substratum stiffness tunes membrane voltage in mammary epithelial cells

Brian B. Silver, Sherry X. Zhang, Emann M. Rabie, Celeste M. Nelson

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numberjcs256313
JournalJournal of cell science
Volume134
Issue number13
DOIs
StatePublished - Jul 2021

All Science Journal Classification (ASJC) codes

  • Cell Biology

Keywords

  • Bioelectricity
  • Mechanical stress
  • Tissue morphodynamics

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