Mechanochemical coupling of lipid organization and protein function through membrane thickness deformations
Mechanochemical coupling of lipid organization and protein function through membrane thickness deformations
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通过膜厚度变形实现脂质组织和蛋白质功能的机械化学耦合
DOI：
10.1103/physreve.105.054410
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发表时间：
2022
影响因子：
2.4
通讯作者：
Haselwandter, Christoph A.
中科院分区：
文献类型：
--
作者：
Shrestha, Ahis;Kahraman, Osman;Haselwandter, Christoph A.
细胞膜由多种蛋白质和脂质组成，具有独特的未受干扰的疏水厚度。为了实现疏水匹配，脂质双层倾向于在膜蛋白周围变形，以匹配双层-蛋白质界面处的蛋白质疏水厚度。这种蛋白质诱导的脂质双层疏水厚度的扭曲会导致大量的能量消耗，这主要取决于双层-蛋白质疏水性失配，而膜蛋白的不同构象状态通常表现出不同的疏水厚度。因此，膜蛋白和脂质之间的疏水相互作用可以产生脂质-蛋白质组织和蛋白质构象状态转变的丰富相互作用。我们将蛋白质诱导的脂质双层厚度变形的膜弹性理论与脂质结构域形成的Landau-Ginzburg理论相结合，系统地探讨了局部脂质组织、脂质和蛋白质疏水性厚度以及具有异质脂质成分的膜中蛋白质诱导的脂质双层厚度变形之间的耦合。我们允许通过蛋白质诱导的脂质双层厚度变形的能量学实现脂质和蛋白质成分的纯机械耦合，以及由特定脂质和蛋白质种类之间的优先相互作用驱动的化学耦合。我们发现，由此产生的脂质蛋白组织可以赋予膜蛋白多样化且受控的机械环境，通过蛋白质诱导的脂质双层厚度变形，可以强烈影响蛋白质功能。这里采用的理论方法为定量预测膜厚度变形如何影响细胞膜中脂质和蛋白质的联合组织和功能提供了总体框架。
Cell membranes are composed of a great variety of protein and lipid species with distinct unperturbed hydrophobic thicknesses. To achieve hydrophobic matching, the lipid bilayer tends to deform around membrane proteins so as to match the protein hydrophobic thickness at bilayer-protein interfaces. Such protein-induced distortions of the lipid bilayer hydrophobic thickness incur a substantial energy cost that depends critically on the bilayer-protein hydrophobic mismatch, while distinct conformational states of membrane proteins often show distinct hydrophobic thicknesses. As a result, hydrophobic interactions between membrane proteins and lipids can yield a rich interplay of lipid-protein organization and transitions in protein conformational state. We combine here the membrane elasticity theory of protein-induced lipid bilayer thickness deformations with the Landau-Ginzburg theory of lipid domain formation to systematically explore the coupling between local lipid organization, lipid and protein hydrophobic thickness, and protein-induced lipid bilayer thickness deformations in membranes with heterogeneous lipid composition. We allow for a purely mechanical coupling of lipid and protein composition through the energetics of protein-induced lipid bilayer thickness deformations as well as a chemical coupling driven by preferential interactions between particular lipid and protein species. We find that the resulting lipid-protein organization can endow membrane proteins with diverse and controlled mechanical environments that, via protein-induced lipid bilayer thickness deformations, can strongly influence protein function. The theoretical approach employed here provides a general framework for the quantitative prediction of how membrane thickness deformations influence the joint organization and function of lipids and proteins in cell membranes.