Domains in biologically relevant lipid membranes

生物学相关脂质膜中的结构域

• 批准号: 183821-2009
• 负责人: Thewalt, Jenifer
• 金额: $ 2.33万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=498074
• 关键词: Domains; biologically; relevant; lipid; membranes

Cells are surrounded by membranes - complex assemblies of lipids and proteins held together by lipids' natural tendency to form bilayers, only two molecules thick, in watery environments. Nearly all biological membranes exist in a liquid crystalline physical state, where membrane components can diffuse within their own layer but typically cannot spontaneously hop to the opposite layer. Membrane lipids have large structural variability and recent evidence suggests that many biological membranes contain domains, distinguishable by both composition and physical characteristics. These domains are often enriched in sphingolipids, which tend in isolation to have relatively high melting temperatures (think of lard compared with olive oil), and sterols such as cholesterol. Based on work with 'model', i.e. protein-free, membranes, such domains are postulated to have a different physical state ("phase"), where the lipids have a more 'orderly' liquid crystalline structure than the surrounding membrane. Long-lived phase coexistence within a membrane strongly influences membrane character: local membrane thickness, diffusion of lipids and proteins within the membrane, interactions between lipids and proteins, and membrane protein function/flexibility could all be affected in cell membranes. We are interested in mapping out the fundamental interactions between phospholipids, sterols and sphingolipids in model membranes, as many of these are poorly understood even though they form the backdrop for interactions among other cell membrane components. Deuterium nuclear magnetic resonance (NMR) is a powerful experimental approach to the study of phase coexistence in membranes: different phases result in clearly distinguishable spectra, and the quantity of labeled lipid in a particular phase can be measured unambiguously. Importantly, deuterium NMR does not rely on large unnatural probes to monitor membrane domains, as even small amounts of such probes can modify domain properties. Knowledge gained from the proposed research will aid cell biologists investigating phenomena related to membrane domains, e.g. programmed cell death, protein localization/signaling, neuronal maturation and bacterial/viral infection.

细胞被膜所包围--膜是由脂质和蛋白质组成的复杂组合体，脂质在水环境中形成双层的自然倾向使它们结合在一起，双层只有两个分子厚。几乎所有的生物膜都以液晶物理状态存在，其中膜组分可以在它们自己的层内扩散，但通常不能自发地跳到相对的层。膜脂具有很大的结构变异性，最近的证据表明，许多生物膜包含域，可通过组成和物理特性进行区分。这些结构域通常富含鞘脂，鞘脂在孤立的情况下往往具有相对较高的熔化温度（想想猪油与橄榄油的比较），以及固醇，如胆固醇。基于对“模型”（即无蛋白质的膜）的研究，假设这些结构域具有不同的物理状态（“相”），其中脂质具有比周围膜更“有序”的液晶结构。膜内的长寿命相共存强烈影响膜特性：局部膜厚度、膜内脂质和蛋白质的扩散、脂质和蛋白质之间的相互作用以及膜蛋白功能/柔性都可能在细胞膜中受到影响。我们有兴趣在模型膜中绘制出磷脂，甾醇和鞘脂之间的基本相互作用，因为其中许多人知之甚少，即使他们形成的背景下，其他细胞膜成分之间的相互作用。氘核磁共振（NMR）是研究膜中相共存的一种强有力的实验方法：不同的相导致清晰可辨的光谱，并且可以明确地测量特定相中标记脂质的量。重要的是，氘NMR不依赖于大的非天然探针来监测膜结构域，因为即使是少量的这种探针也可以改变结构域的性质。从拟议的研究中获得的知识将有助于细胞生物学家研究与膜结构域相关的现象，例如程序性细胞死亡，蛋白质定位/信号传导，神经元成熟和细菌/病毒感染。