Lipid demixing and protein-protein interactions in the adsorption of charged proteins on mixed membranes
Lipid demixing and protein-protein interactions in the adsorption of charged proteins on mixed membranes
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DOI：
10.1016/s0006-3495(00)76427-7
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发表时间：
2000-10-01
影响因子：
3.4
通讯作者：
Ben-Shaul, A
中科院分区：
文献类型：
--
作者：
May, S;Harries, D;Ben-Shaul, A
混合膜上的带电蛋白质的吸附自由能，含有不同量的（相反）带电荷的脂质，计算的基础上的平均场自由能表达式，明确说明的能力的脂质局部分层，和横向之间的相互作用吸附的蛋白质。这种自由能泛函的最小化产生了熟悉的非线性Poisson-Boltzmann方程和允许脂质电荷重排的膜表面的边界条件。这两个自洽方程同时求解。蛋白质被建模为均匀带电的球体和（裸）膜作为一个理想的二维二元混合物的带电和中性脂质。当高电荷的蛋白质吸附在弱电荷的膜上时，发现脂质电荷密度分布的实质性变化;脂质在一定的分层熵罚下，调整它们在吸附的蛋白质附近的浓度以实现最佳的电荷匹配。被吸附的蛋白质之间的侧向排斥相互作用影响脂质调节曲线，并且在高密度下，导致结合能的大幅降低。吸附等温线表明脂质流动性和蛋白质-蛋白质相互作用的重要性，使用吸附方程与覆盖依赖性结合常数计算。通常，在体-表面平衡（即，当膜表面被吸附的蛋白质“饱和”时），膜电荷被蛋白质电荷“过度补偿”，因为只有大约一半的蛋白质电荷（面对膜的半球上的那些）参与电荷中和。最后，有人认为，蛋白质的静电吸附可能会增强脂质-蛋白质结构域的形成，但其起源（例如，与脂质分层有关的弹性变形）不是纯粹的静电。
The adsorption free energy of charged proteins on mixed membranes, containing varying amounts of (oppositely) charged lipids, is calculated based on a mean-field free energy expression that accounts explicitly for the ability of the lipids to demix locally, and for lateral interactions between the adsorbed proteins. Minimization of this free energy functional yields the familiar nonlinear Poisson-Boltzmann equation and the boundary condition at the membrane surface that allows for lipid charge rearrangement. These two self-consistent equations are solved simultaneously. The proteins are modeled as uniformly charged spheres and the (bare) membrane as an ideal two-dimensional binary mixture of charged and neutral lipids. Substantial variations in the lipid charge density profiles are found when highly charged proteins adsorb on weakly charged membranes; the lipids, at a certain demixing entropy penalty, adjust their concentration in the vicinity of the adsorbed protein to achieve optimal charge matching. Lateral repulsive interactions between the adsorbed proteins affect the lipid modulation profile and, at high densities, result in substantial lowering of the binding energy. Adsorption isotherms demonstrating the importance of lipid mobility and protein-protein interactions are calculated using an adsorption equation with a coverage-dependent binding constant. Typically, at bulk-surface equilibrium (i.e., when the membrane surface is "saturated" by adsorbed proteins), the membrane charges are "overcompensated" by the protein charges, because only about half of the protein charges (those on the hemispheres facing the membrane) are involved in charge neutralization. Finally, it is argued that the formation of lipid-protein domains may be enhanced by electrostatic adsorption of proteins, but its origin (e.g., elastic deformations associated with lipid demixing) is not purely electrostatic.