Department of Mechanical Engineering, Washington University, St. Louis, Missouri 63130, USA.
Department of Physics, Washington University, St. Louis, Missouri 63130, USA.
Phys Rev E. 2017 May;95(5-1):052414. doi: 10.1103/PhysRevE.95.052414. Epub 2017 May 23.
Clathrin-mediated endocytosis in yeast is driven by a protein patch containing close to 100 different types of proteins. Among the proteins are 5000-10000 copies of polymerized actin, and successful endocytosis requires growth of the actin network. Since it is not known exactly how actin network growth drives endocytosis, we calculate the spatial distribution of actin growth required to generate the force that drives the process. First, we establish the force distribution that must be supplied by actin growth, by combining membrane-bending profiles obtained via electron microscopy with established theories of membrane mechanics. Next, we determine the profile of actin growth, using a continuum mechanics approach and an iterative procedure starting with an actin growth profile obtained from a linear analysis. The profile has fairly constant growth outside a central hole of radius 45-50 nm, but very little growth in this hole. This growth profile can reproduce the required forces if the actin shear modulus exceeds 80 kPa, and the growing filaments can exert very large polymerization forces. The growth profile prediction could be tested via electron-microscopy or super-resolution experiments in which the turgor pressure is suddenly turned off.
网格蛋白介导的胞吞作用在酵母中由一个包含近 100 种不同类型蛋白质的蛋白斑块驱动。这些蛋白质中有 5000-10000 个聚合肌动蛋白分子,成功的胞吞作用需要肌动蛋白网络的生长。由于目前尚不清楚肌动蛋白网络的生长是如何驱动胞吞作用的,我们计算了产生驱动该过程的力所需的肌动蛋白生长的空间分布。首先,我们通过将电子显微镜获得的膜弯曲轮廓与已建立的膜力学理论相结合,确定了由肌动蛋白生长提供的力的分布。接下来,我们使用连续介质力学方法和从线性分析中获得的肌动蛋白生长轮廓的迭代过程来确定肌动蛋白生长的轮廓。在半径为 45-50nm 的中心孔之外,生长轮廓具有相当稳定的生长,但在这个孔内几乎没有生长。如果肌动蛋白切变模量超过 80kPa,并且生长的纤维可以产生非常大的聚合力,那么这种生长轮廓可以再现所需的力。可以通过电子显微镜或超分辨率实验来检验生长轮廓的预测,在这些实验中,渗透压会突然关闭。