Abney J R, Scalettar B A
Department of Physics, Lewis and Clark College, Portland, OR 97219, USA.
Biophys Chem. 1995 Dec;57(1):27-36. doi: 10.1016/0301-4622(95)00042-v.
Biological membranes contain many specialized domains, ranging from tens of nanometers to several microns in size and characterized by different concentrations and compositions of protein. Because these domains influence membrane function, considerable attention has focused on understanding their origin. Here it is shown that number fluctuations and nonspecific interprotein interactions can lead to considerable heterogeneity in the distribution of membrane proteins, and to an associated submicron-scale domain structure. Number fluctuations were analyzed by modeling the membrane as a two-dimensional fluid containing interacting protein solutes. The characteristic size and lifetime of a domain in which one would expect to observe a fluctuation of specified magnitude was calculated; snapshots showing fluctuation-induced heterogeneity were generated by Monte Carlo simulation. Domain size was found to depend on the nature of the interprotein force (e.g., attractive or repulsive) and on the average protein concentration. Domain size was largest at low protein concentrations and in the presence of attractive interprotein forces, and was smallest at high protein concentrations and in the presence of repulsive interprotein forces. Domain lifetime was found to depend on domain size and on the diffusion coefficient of the proteins. In a 'typical' membrane containing 5-nm proteins with diffusion coefficient 10(-10) cm(2)/s at a density of 1000 proteins/microm(2), a 30% fluctuation will yield domains characterized by a 2-fold difference in local concentration; these domains persist over a distance of about 100 nm and have a lifetime of about 0.25 s. These results can be used to analyze the domain structure commonly observed in electron micrographs, and have implications for both number fluctuation and Monte Carlo studies of the distribution and dynamics of membrane proteins.
生物膜包含许多特殊区域，其大小从几十纳米到几微米不等，且具有不同的蛋白质浓度和组成。由于这些区域会影响膜的功能，因此人们相当关注对其起源的理解。本文表明，数量波动和非特异性蛋白质间相互作用会导致膜蛋白分布出现显著的异质性，并形成相关的亚微米级区域结构。通过将膜模拟为包含相互作用蛋白质溶质的二维流体来分析数量波动。计算了预期会观察到特定幅度波动的区域的特征尺寸和寿命；通过蒙特卡罗模拟生成了显示波动诱导异质性的快照。发现区域大小取决于蛋白质间作用力的性质（例如吸引或排斥）以及平均蛋白质浓度。在低蛋白质浓度且存在吸引性蛋白质间作用力的情况下，区域大小最大；而在高蛋白质浓度且存在排斥性蛋白质间作用力的情况下，区域大小最小。发现区域寿命取决于区域大小和蛋白质的扩散系数。在一个“典型”的膜中，含有直径为5纳米、扩散系数为10^(-10) 平方厘米/秒、密度为1000个蛋白质/微米² 的蛋白质，30% 的波动会产生局部浓度相差2倍的区域；这些区域在约100纳米的距离内持续存在，寿命约为0.25秒。这些结果可用于分析电子显微镜照片中常见的区域结构，并且对膜蛋白分布和动力学的数量波动及蒙特卡罗研究都有启示意义。
