近日，美国哈佛医学院Markus Basan及其团队的研究发现膜电位介导细胞对机械压力的反应。相关论文于2025年12月2日发表在《细胞》杂志上。

该课题组证明膜电位是细胞对机械压力反应的重要介质。该课题组研究人员表明，作用于细胞的机械力改变了细胞的生物量密度，这反过来又改变了膜电位。然后，膜电位通过控制细胞生长、增殖和细胞消除来调节上皮细胞的数量密度。从机制上讲，课题组表明通过Hippo和丝裂原活化蛋白激酶（MAPK）途径以及潜在的起源于细胞膜的其他信号通路，膜电位控制信号通路的变化。虽然已知许多分子相互作用会影响Hippo信号传导，但激活膜上典型Hippo通路的上游信号此前一直是未知的。他们的研究结果表明，膜电位是生长和组织稳态的重要调节因子。

据悉，机械力通过很大程度上神秘的机制影响细胞生长、死亡或分化的决定。另外，静息膜电位的变化在发育、分化、再生和癌症中也被观察到。

附：英文原文

Title: Membrane potential mediates the cellular response to mechanical pressure

Author: Avik Mukherjee, Yanqing Huang, Jens Elgeti, Seungeun Oh, Jose G. Abreu, Leander Ammar, Anjali R. Neliat, Janik Schüttler, Dan-Dan Su, Christophe Dupre, Nina Catherine Benites, Xili Liu, Leonid Peshkin, Mihail Barboiu, Hugo Stocker, Marc W. Kirschner, Markus Basan

Issue&Volume: 2025-12-02

Abstract: Mechanical forces influence cellular decisions to grow, die, or differentiate, through largely mysterious mechanisms. Separately, changes in resting membrane potential have been observed in development, differentiation, regeneration, and cancer. We demonstrate that membrane potential is an important mediator of cellular response to mechanical pressure. We show that mechanical forces acting on the cell change cellular biomass density, which, in turn, alters membrane potential. Membrane potential then regulates cell number density in epithelia by controlling cell growth, proliferation, and cell elimination. Mechanistically, we show that changes in membrane potential control signaling through the Hippo and mitogen-activated protein kinase (MAPK) pathways and potentially other signaling pathways that originate at the cell membrane. While many molecular interactions are known to affect Hippo signaling, the upstream signal that activates the canonical Hippo pathway at the membrane has previously been elusive. Our results establish membrane potential as an important regulator of growth and tissue homeostasis.

DOI: 10.1016/j.cell.2025.11.004

Source: https://www.cell.com/cell/abstract/S0092-8674(25)01253-X