Sarkis Joe, Vié Véronique
Department of Cell Biology, Harvard Medical School and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.
Univ Rennes, CNRS, IPR-UMR 6251, Rennes, France.
Front Bioeng Biotechnol. 2020 Apr 15;8:270. doi: 10.3389/fbioe.2020.00270. eCollection 2020.
Biological membranes are highly dynamic in their ability to orchestrate vital mechanisms including cellular protection, organelle compartmentalization, cellular biomechanics, nutrient transport, molecular/enzymatic recognition, and membrane fusion. Controlling lipid composition of different membranes allows cells to regulate their membrane characteristics, thus modifying their physical properties to permit specific protein interactions and drive structural function (membrane deformation facilitates vesicle budding and fusion) and signal transduction. Yet, how lipids control protein structure and function is still poorly understood and needs systematic investigation. In this review, we explore different membrane models and summarize our current understanding of the interplay between membrane biophysical properties and lipid-protein interaction, taken as example few proteins involved in muscular activity (dystrophin), digestion and Legionella pneumophila effector protein DrrA. The monolayer model with its movable barriers aims to mimic any membrane deformation while surface pressure modulation imitates lipid packing and membrane curvature changes. It is frequently used to investigate peripheral protein binding to the lipid headgroups. Examples of how lipid lateral pressure modifies protein interaction and organization within the membrane are presented using various biophysical techniques. Interestingly, the shear elasticity and surface viscosity of the monolayer will increase upon specific protein(s) binding, supporting the importance of such mechanical link for membrane stability. The lipid bilayer models such as vesicles are not only used to investigate direct protein binding based on the lipid nature, but more importantly to assess how local membrane curvature (vesicles with different size) influence the binding properties of a protein. Also, supported lipid bilayer model has been used widely to characterize diffusion law of lipids within the bilayer and/or protein/biomolecule binding and diffusion on the membrane. These membrane models continue to elucidate important advances regarding the dynamic properties harmonizing lipid-protein interaction.
生物膜在协调重要机制方面具有高度动态性，这些机制包括细胞保护、细胞器区室化、细胞生物力学、营养物质运输、分子/酶识别以及膜融合。控制不同膜的脂质组成可使细胞调节其膜特性，从而改变其物理性质，以允许特定的蛋白质相互作用并驱动结构功能（膜变形促进囊泡出芽和融合）以及信号转导。然而，脂质如何控制蛋白质结构和功能仍知之甚少，需要进行系统研究。在本综述中，我们探讨了不同的膜模型，并总结了我们目前对膜生物物理性质与脂质 - 蛋白质相互作用之间相互作用的理解，以参与肌肉活动的几种蛋白质（肌营养不良蛋白）、消化和嗜肺军团菌效应蛋白DrrA为例。具有可移动屏障的单层模型旨在模拟任何膜变形，而表面压力调节则模仿脂质堆积和膜曲率变化。它经常用于研究外周蛋白与脂质头部基团的结合。使用各种生物物理技术展示了脂质侧向压力如何改变膜内蛋白质相互作用和组织的示例。有趣的是，单层的剪切弹性和表面粘度在特定蛋白质结合后会增加，这支持了这种机械联系对膜稳定性的重要性。脂质双层模型如囊泡不仅用于研究基于脂质性质的直接蛋白质结合，更重要的是评估局部膜曲率（不同大小的囊泡）如何影响蛋白质的结合特性。此外，支持的脂质双层模型已被广泛用于表征双层内脂质的扩散规律和/或蛋白质/生物分子在膜上的结合和扩散。这些膜模型继续阐明了关于协调脂质 - 蛋白质相互作用的动态特性的重要进展。
