Reduced Lateral Mobility of Lipids and Proteins in Crowded Membranes

Coarse-grained molecular dynamics simulations of the E. coli outer membrane proteins FhuA, LamB, NanC, OmpA and OmpF in a POPE/POPG (3∶1) bilayer were performed to characterise the diffusive nature of each component of the membrane. At small observation times (50 ns) of 8.5×10−7 cm2 s−1. The phospholipid diffusion around each protein was found to vary based on distance from protein. An asymmetry in the diffusion of annular lipids in the inner and outer leaflets was observed and correlated with an asymmetry in charged residues in the vicinity of the inner and outer leaflet head-groups. Protein rotational and translational diffusion were also found to vary with observation time and were inversely correlated with the radius of gyration of the protein in the plane of the bilayer. As the concentration of protein within the bilayer was increased, the overall mobility of the membrane decreased reflected in reduced lipid diffusion coefficients for both lipid and protein components. The increase in protein concentration also resulted in a decrease in the anomalous diffusion exponent α of the lipid. Formation of extended clusters and networks of proteins led to compartmentalisation of lipids in extreme cases.

本研究针对大肠杆菌（E. coli）外膜蛋白FhuA、LamB、NanC、OmpA及OmpF，在磷脂酰乙醇胺/磷脂酰甘油（POPE/POPG，摩尔比3∶1）双层膜体系中开展粗粒度分子动力学（coarse-grained molecular dynamics）模拟，以表征该膜各组分的扩散特性。在50 ns的短观测时长下，脂质扩散系数为8.5×10⁻⁷ cm²·s⁻¹。研究发现，各蛋白周围的磷脂扩散速率随与蛋白的距离变化而改变。本研究观测到内膜小叶与外膜小叶周围的环形脂质扩散存在不对称性，且该不对称性与内外小叶头部基团附近带电残基的分布不对称性相关。同时发现，蛋白的旋转与平移扩散速率同样随观测时长变化，且与该蛋白在双层膜平面内的回转半径呈负相关。随着双层膜内蛋白浓度升高，膜整体流动性降低，具体表现为脂质与蛋白组分的扩散系数均下降。蛋白浓度升高还会导致脂质的反常扩散指数α降低。在极端情况下，蛋白形成的延展团簇与网络结构会引发脂质的区域化分隔。