Lipid plasticity and its relevance for critical biological processes involving membrane reorganization

细胞膜对生命具有独特的重要性，因为它是细胞环境的屏障，控制着什么进入什么离开。此外，通过融合和裂变进行的膜重组是许多生物过程的核心，如受精、病毒感染、囊泡运输和细胞分裂。细胞膜主要由构成细胞膜框架的脂质和负责生物活动的蛋白质组成，如酶促过程。磷脂是自然界中发现的最重要的一类脂质。这些分子是两亲性的，即它们有亲水性部分，通常称为极性头，以及由两条脂肪链组成的疏水性部分。当磷脂与足够浓度的水混合时，疏水力使脂肪链重新组合在一起，极性头面向水。生物膜主要以双层结构排列。此外，具有疏水性的蛋白质与膜结合。我们小组最近的工作表明，嵌入在双分子层中的肽具有改变脂质构象或“形状”的能力。基于这种肽诱导的脂质效应，我们提出了“动态诱导形状”的概念。这个概念认识到双层膜是一个构象塑性和动态环境，以复杂的方式对杂质或物理应力的存在作出反应。该研究计划的主要目的是研究两种高生物学相关性的情况下的膜可塑性，即病毒感染引起的膜融合和抗菌肽引起的膜裂变。结构生物信息学的补充工具将用于实现这一创新研究计划的目标。

The cell membrane is of singular importance for life since it acts as a barrier to the cell environment and controls what goes in and what goes out. Moreover, membrane reorganization by fusion and fission is central to a number of biological processes, such as fertilization, viral infection, vesicle trafficking and cell division. Cell membranes are mainly composed of lipids, forming the framework of the membranes, and proteins, responsible for the biological activities, such as enzymatic processes. The phospholipids constitute the most important class of lipids found in Nature. These molecules are amphipatic, i.e. they have a hydrophilic part, commonly called the polar head, and a hydrophobic part composed of two aliphatic chains. When phospholipids are mixed with water in adequate concentrations, hydrophobic forces cause the aliphatic chains regroup together with the polar heads facing the water. Biological membranes are predominantly arranged as bilayers. Also, proteins with a hydrophobic nature bind to membranes. Recent work from our group shown that a peptide embedded in a bilayer has the ability to change the conformation or "shape" of the lipids. Based on this peptide-induced effect on the lipids, we then proposed the concept of "dynamically induced shape". This concept recognizes that the bilayer membrane is a conformationally plastic and dynamical environment that reacts in a complex way to the presence of impurities or a physical stress. The main objective of the proposed research program is to investigate membrane plasticity for two cases of high biological relevance, membrane fusion from viral infection and membrane fission by antimicrobial peptides. Complementary tools from structural bioinformatics will be used to achieve the goals of this innovative research program.