Sakamoto Ken, Akimoto Takuma, Muramatsu Mayu, Sansom Mark S P, Metzler Ralf, Yamamoto Eiji
Department of System Design Engineering, Keio University, Yokohama, Kanagawa 223-8522, Japan.
Department of Physics, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
PNAS Nexus. 2023 Aug 3;2(8):pgad258. doi: 10.1093/pnasnexus/pgad258. eCollection 2023 Aug.
Cell membranes phase separate into ordered and disordered domains depending on their compositions. This membrane compartmentalization is heterogeneous and regulates the localization of specific proteins related to cell signaling and trafficking. However, it is unclear how the heterogeneity of the membranes affects the diffusion and localization of proteins in and domains. Here, using Langevin dynamics simulations coupled with the phase-field (LDPF) method, we investigate several tens of milliseconds-scale diffusion and localization of proteins in heterogeneous biological membrane models showing phase separation into and domains. The diffusivity of proteins exhibits temporal fluctuations depending on the field composition. Increases in molecular concentrations and domain preference of the molecule induce subdiffusive behavior due to molecular collisions by crowding and confinement effects, respectively. Moreover, we quantitatively demonstrate that the protein partitioning into the domain is determined by the difference in molecular diffusivity between domains, molecular preference of domain, and molecular concentration. These results pave the way for understanding how biological reactions caused by molecular partitioning may be controlled in heterogeneous media. Moreover, the methodology proposed here is applicable not only to biological membrane systems but also to the study of diffusion and localization phenomena of molecules in various heterogeneous systems.
细胞膜根据其组成相分离为有序和无序区域。这种膜区室化是异质的，并调节与细胞信号传导和运输相关的特定蛋白质的定位。然而，尚不清楚膜的异质性如何影响蛋白质在有序和无序区域中的扩散和定位。在这里，我们使用结合相场的朗之万动力学模拟（LDPF）方法，研究了在显示相分离为有序和无序区域的异质生物膜模型中蛋白质几十毫秒尺度的扩散和定位。蛋白质的扩散率表现出随场组成的时间波动。分子浓度的增加和分子对区域的偏好分别由于拥挤和限制效应引起的分子碰撞而导致亚扩散行为。此外，我们定量证明蛋白质在有序区域中的分配由区域间分子扩散率的差异、分子对区域的偏好和分子浓度决定。这些结果为理解分子分配引起的生物反应如何在异质介质中得到控制铺平了道路。此外，这里提出的方法不仅适用于生物膜系统，也适用于研究各种异质系统中分子的扩散和定位现象。
