Bonilla-Quintana Mayte, Ghisleni Andrea, Gauthier Nils C, Rangamani Padmini
Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla, CA 92093, USA.
Institute FIRC of Molecular Oncology (IFOM), Via Adamello 16, 20139 Milan, Italy.
J Cell Sci. 2025 Feb 15;138(4). doi: 10.1242/jcs.263473. Epub 2025 Feb 28.
The plasma membrane and the underlying skeleton form a protective barrier for eukaryotic cells. The molecular players forming this complex composite material constantly rearrange under mechanical stress. One of those molecules, spectrin, is ubiquitous in the membrane skeleton and linked by short actin filaments. In this work, we developed a generalized network model for the membrane skeleton integrating myosin contractility and membrane mechanics to investigate the response of the spectrin meshwork to mechanical loading. We observed that the force generated by membrane bending is important in maintaining a regular skeletal structure, suggesting that the membrane is not just supported by the skeleton, but actively contributes towards the stability of the cell structure. We found that spectrin and myosin turnover are necessary for the transition between stress and rest states in the skeleton. Simulations of a fully connected network representing a whole cell show that the surface area constraint of the plasma membrane and volume restriction of the cytoplasm enhance the stability of the membrane skeleton. Furthermore, we showed that cell attachment through adhesions promotes cell shape stabilization.
质膜及其下方的骨架为真核细胞形成了一道保护屏障。构成这种复杂复合材料的分子成分在机械应力作用下不断重新排列。其中一种分子,血影蛋白,在膜骨架中普遍存在,并由短肌动蛋白丝连接。在这项工作中,我们开发了一个整合肌球蛋白收缩性和膜力学的膜骨架广义网络模型,以研究血影蛋白网络对机械负荷的响应。我们观察到,膜弯曲产生的力对于维持规则的骨架结构很重要,这表明膜不仅由骨架支撑,还积极有助于细胞结构的稳定性。我们发现,血影蛋白和肌球蛋白的周转对于骨架中应力状态和静止状态之间的转变是必要的。对代表整个细胞的全连接网络的模拟表明,质膜的表面积限制和细胞质的体积限制增强了膜骨架的稳定性。此外,我们表明通过黏附进行的细胞附着促进了细胞形状的稳定。