Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712.
Department of Mechanical and Aerospace Engineering, University of California San Diego, San Diego, CA 92093.
Proc Natl Acad Sci U S A. 2021 Mar 16;118(11). doi: 10.1073/pnas.2017435118.
Membrane bending is a ubiquitous cellular process that is required for membrane traffic, cell motility, organelle biogenesis, and cell division. Proteins that bind to membranes using specific structural features, such as wedge-like amphipathic helices and crescent-shaped scaffolds, are thought to be the primary drivers of membrane bending. However, many membrane-binding proteins have substantial regions of intrinsic disorder which lack a stable three-dimensional structure. Interestingly, many of these disordered domains have recently been found to form networks stabilized by weak, multivalent contacts, leading to assembly of protein liquid phases on membrane surfaces. Here we ask how membrane-associated protein liquids impact membrane curvature. We find that protein phase separation on the surfaces of synthetic and cell-derived membrane vesicles creates a substantial compressive stress in the plane of the membrane. This stress drives the membrane to bend inward, creating protein-lined membrane tubules. A simple mechanical model of this process accurately predicts the experimentally measured relationship between the rigidity of the membrane and the diameter of the membrane tubules. Discovery of this mechanism, which may be relevant to a broad range of cellular protrusions, illustrates that membrane remodeling is not exclusive to structured scaffolds but can also be driven by the rapidly emerging class of liquid-like protein networks that assemble at membranes.
膜弯曲是一种普遍存在的细胞过程，对于膜运输、细胞运动、细胞器发生和细胞分裂都是必需的。使用特定结构特征（如楔形两亲性螺旋和新月形支架）与膜结合的蛋白质被认为是膜弯曲的主要驱动因素。然而，许多膜结合蛋白具有大量的无规则区域，缺乏稳定的三维结构。有趣的是，这些无规区域中的许多最近被发现形成由弱多价接触稳定的网络，导致在膜表面上组装蛋白质液相对。在这里，我们询问膜相关蛋白液体如何影响膜曲率。我们发现，在合成和细胞衍生的膜泡表面上的蛋白质相分离在膜的平面中产生了相当大的压缩应力。这种应力驱动膜向内弯曲，形成由蛋白质排列的膜小管。该过程的简单力学模型准确地预测了实验测量的膜刚性与膜小管直径之间的关系。这种机制的发现可能与广泛的细胞突起有关，它表明膜重塑不仅限于结构支架，而且还可以由在膜上组装的快速出现的类液体状蛋白质网络驱动。
