Rafts as Curvature-Induced Microemulsions

作为曲率诱导微乳液的筏

• 批准号: 1203282
• 负责人: Michael Schick
• 金额: $ 33万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1203282&HistoricalAwards=false
• 关键词: Rafts; Curvature; Induced; Microemulsions

TECHNICAL SUMMARYThis award supports theoretical research and education to investigate physical mechanisms leading to the organization of lipid membranes. The idea that the plasma membrane is not uniform but displays physical organization which leads to functional organization is one that has attracted enormous attention. This is due to the fact that such organization would affect a host of biologically important processes, such as signaling, endocytosis, membrane fusion, and viral entry, among many others. In spite of the compelling nature of the hypothesis, and of the ever-increasing evidence, there remains skepticism concerning the idea. The PI will investigate a mechanism that arises from the well-known variety in lipid composition of the inner and outer leaves of the plasma membrane. It has been hypothesized that differences in composition between the leaves can couple to the curvature of the membrane, with unsaturated lipids preferring regions in which the membrane bulges outward, and saturated lipids and cholesterol preferring regions on the opposite leaf where the membrane bulges inward. It was known that such coupling can, in principle, bring about modulated phases, such as those displaying alternating stripes. But these phases are not seen in biological systems. These same forces can also induce a curvature-induced microemulsion, with droplets whose area is characterized by the ratio of the bending modulus to the surface tension. These droplets would form and break up dynamically. The PI will use theoretical and computational methods to develop this idea and to enable experimentalists to test the existence of such two-dimensional microemulsions. NONTECHNICAL SUMMARY This award supports theoretical research and education to investigate a physical mechanism for how the molecules in cell walls organize themselves. Proteins are the machines which carry out innumerable crucial functions in our body. Some are found on the outside of cells, others on the inside. In general it takes many different proteins working together to carry out some particular function. How do proteins on one side of the cell wall communicate with one another, and how do they communicate with proteins on the other side of the cell wall? It used to be thought that the proteins were distributed randomly over the cell surface so it was only by chance meetings that they found one another. And for a protein on one side of the cell wall to be positioned near one on the opposite side, that too was a matter of chance. More recently it has been suggested that this picture is incorrect. Instead it has been proposed that the molecules which make up the cell wall form distinct regions; the molecules with carbon tails that have no double bonds, like 'saturated fats,' form small regions with the molecule cholesterol. These regions float like rafts in a sea of molecules with carbon tails that do have double bonds, like 'unsaturated fats.' Proteins on either side of the cell wall are anchored to it, and these anchors can distinguish the rafts from the sea, and prefer to be in one or the other. In this picture, then, the distribution of proteins is not random; those that prefer the rafts are close together as are those that prefer the sea. This is very appealing but it leaves open one important question; why do these molecules aggregate into rafts and sea in the first place? The PI and collaborators are exploring the idea that undulations of the cell wall tend to organize the molecules comprising it much as waves in the ocean affect the seaweed floating on it, driving them apart at wave crests and pushing them together at wave troughs.

技术总结该奖项支持理论研究和教育，以调查导致类脂膜组织的物理机制。质膜不是均匀的，但表现为物理组织，从而导致功能组织，这一观点引起了人们的极大关注。这是因为这样的组织会影响许多重要的生物学过程，如信号传递、内吞作用、膜融合和病毒进入等。尽管这一假设的性质令人信服，而且证据越来越多，但人们仍然对这一想法持怀疑态度。PI将研究质膜内外叶的脂类成分的众所周知的变化所产生的机制。有人假设，叶片之间的组成差异可能与膜的曲率有关，不饱和脂更喜欢膜向外膨胀的区域，而饱和脂和胆固醇更喜欢相反叶片上膜向内隆起的区域。众所周知，这种耦合在原则上可以产生调制相位，例如那些显示交替条纹的相位。但这些阶段在生物系统中是不存在的。这些相同的力也可以诱导曲率诱导的微乳液，液滴的面积由弯曲模数与表面张力的比率来表征。这些液滴会动态地形成和分解。PI将使用理论和计算方法来发展这一想法，并使实验者能够测试这种二维微乳液的存在。非技术总结该奖项支持理论研究和教育，以研究细胞壁中分子如何自我组织的物理机制。蛋白质是在我们体内执行无数重要功能的机器。一些在细胞的外部，另一些在细胞的内部。一般说来，需要许多不同的蛋白质协同工作才能完成某些特定的功能。细胞壁一侧的蛋白质是如何相互沟通的，它们又是如何与细胞壁另一侧的蛋白质沟通的？过去人们认为，蛋白质是随机分布在细胞表面的，所以它们只是偶然相遇，才找到了彼此。而对于细胞壁一侧的蛋白质靠近另一侧的蛋白质来说，这也是一个机会问题。最近，有人暗示这幅图景是不正确的。相反，有人提出，构成细胞壁的分子形成不同的区域；没有双键的碳尾分子，如饱和脂肪，与胆固醇分子形成小区域。这些区域就像漂浮在分子海洋中的木筏，分子的尾巴确实有双键，比如不饱和脂肪。细胞壁两边的蛋白质都被锚定在上面，这些锚定可以区分木筏和海洋，并倾向于在其中之一。因此，在这张图中，蛋白质的分布并不是随机的；那些喜欢木筏的人和那些喜欢大海的人一样，靠得很近。这很吸引人，但它留下了一个重要的问题：为什么这些分子一开始会聚集成木筏和大海？PI及其合作者正在探索这样一种观点，即细胞壁的起伏往往会将构成细胞壁的分子组织起来，就像海洋中的波浪影响漂浮在细胞壁上的海藻一样，在波峰时将它们分开，在波谷时将它们推到一起。