Epithelial tissue geometry directs emergence of bioelectric field and pattern of proliferation

Molecular Biology of the Cell
Brian B SilverCeleste M Nelson

Abstract

Patterns of proliferation are templated by both gradients of mechanical stress as well as by gradients in membrane voltage (Vm), which is defined as the electric potential difference between the cytoplasm and the extracellular medium. Either gradient could regulate the emergence of the other, or they could arise independently and synergistically affect proliferation within a tissue. Here, we examined the relationship between endogenous patterns of mechanical stress and the generation of bioelectric gradients in mammary epithelial tissues. We observed that the mechanical stress gradients in the tissues presaged gradients in both proliferation and depolarization, consistent with previous reports correlating depolarization with proliferation. Furthermore, disrupting the Vm gradient blocked the emergence of patterned proliferation. We found that the bioelectric gradient formed downstream of mechanical stresses within the tissues and depended on connexin-43 (Cx43) hemichannels, which opened preferentially in cells located in regions of high mechanical stress. Activation of Cx43 hemichannels was necessary for nuclear localization of Yap/Taz and induction of proliferation. Together, these results suggest that mechanotransduction trigg...Continue Reading

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Citations

Nov 5, 2020·Biomechanics and Modeling in Mechanobiology·Alessandro Leronni
Apr 24, 2021·Advanced Healthcare Materials·Ian C BergGregory H Underhill
May 8, 2021·Progress in Biophysics and Molecular Biology·Michael Levin
May 13, 2021·Stem Cell Reports·Ananya GuptaKatharina F Sonnen
Jun 29, 2021·IScience·Ting-Xin JiangCheng-Ming Chuong
Jul 17, 2021·Frontiers in Cell and Developmental Biology·Yiju Wei, Wei Li
Jul 28, 2021·Journal of Cell Science·Brian B SilverCeleste M Nelson

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Methods Mentioned

BETA
nuclear translocation
fluorescence recovery after photobleaching
transfection
Assay
fluorescence microscopy

Software Mentioned

Imaris
ImageJ

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