Houser Justin R, Busch David J, Bell David R, Li Brian, Ren Pengyu, Stachowiak Jeanne C
Department of Biomedical Engineering, The University of Texas at Austin, TX, Austin, USA.
Soft Matter. 2016 Feb 21;12(7):2127-34. doi: 10.1039/c5sm02572a. Epub 2016 Jan 11.
Diffusion of transmembrane and peripheral membrane-bound proteins within the crowded cellular membrane environment is essential to diverse biological processes including cellular signaling, endocytosis, and motility. Nonetheless we presently lack a detailed understanding of the influence of physiological levels of crowding on membrane protein diffusion. Utilizing quantitative in vitro measurements, here we demonstrate that the diffusivities of membrane bound proteins follow a single linearly decreasing trend with increasing membrane coverage by proteins. This trend holds for homogenous protein populations across a range of protein sizes and for heterogeneous mixtures of proteins of different sizes, such that protein diffusivity is controlled by the total coverage of the surrounding membrane. These results demonstrate that steric exclusion within the crowded membrane environment can fundamentally limit the diffusive rate of proteins, regardless of their size. In cells this "speed limit" could be modulated by changes in local membrane coverage, providing a mechanism for tuning the rate of molecular interaction and assembly.
跨膜蛋白和外周膜结合蛋白在拥挤的细胞膜环境中的扩散对于包括细胞信号传导、内吞作用和运动性在内的多种生物学过程至关重要。然而，目前我们对生理水平的拥挤对膜蛋白扩散的影响仍缺乏详细了解。通过定量体外测量，我们在此证明膜结合蛋白的扩散系数随蛋白质对膜的覆盖率增加呈单一的线性下降趋势。这一趋势适用于各种蛋白质大小的均匀蛋白质群体以及不同大小蛋白质的异质混合物，因此蛋白质扩散系数由周围膜的总覆盖率控制。这些结果表明，拥挤的膜环境中的空间排斥从根本上限制了蛋白质的扩散速率，无论其大小如何。在细胞中，这种“速度限制”可以通过局部膜覆盖率的变化来调节，从而提供一种调节分子相互作用和组装速率的机制。
