Rafts as Curvature-Induced Microemulsions

该奖项支持理论研究和教育，以调查导致脂质膜组织的物理机制。质膜不是均匀的，而是表现出物理组织，从而导致功能组织的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，如信号传导、内吞作用、膜融合和病毒进入等。尽管这一假设具有令人信服的性质，证据也越来越多，但人们对这一观点仍持怀疑态度。PI将研究一种机制，这种机制源于质膜内外叶中众所周知的脂质组成的变化。据推测，叶片之间的成分差异可能与膜的曲率有关，不饱和脂质倾向于膜向外凸起的区域，而饱和脂质和胆固醇倾向于膜向内凸起的相反叶片上的区域。众所周知，这种耦合在原则上可以产生调制相位，例如显示交替条纹的相位。但是这些阶段在生物系统中是看不到的。这些相同的力也可以诱导曲率诱导的微乳液，其液滴的面积由弯曲模量与表面张力的比值表征。这些液滴会动态地形成和破裂。PI将使用理论和计算方法来发展这一想法，并使实验家能够测试这种二维微乳剂的存在。该奖项支持理论研究和教育，以调查细胞壁分子如何组织自己的物理机制。蛋白质是在我们体内执行无数关键功能的机器。有些在细胞外部，有些在细胞内部。一般来说，需要许多不同的蛋白质协同工作来完成某些特定的功能。细胞壁一侧的蛋白质是如何相互交流的，它们又是如何与细胞壁另一侧的蛋白质交流的？过去人们认为蛋白质在细胞表面是随机分布的，只有偶然相遇才能找到彼此。对于细胞壁一侧的蛋白质来说，要靠近另一侧的蛋白质，这也是一个偶然的问题。最近有人提出，这种看法是不正确的。相反，有人提出，构成细胞壁的分子形成不同的区域；碳末端没有双键的分子，如“饱和脂肪”，与胆固醇分子形成小区域。这些区域像木筏一样漂浮在分子海洋中，碳尾巴确实有双键，比如“不饱和脂肪”。细胞壁两侧的蛋白质都被锚定在上面，这些锚定可以将木筏与海洋区分开来，并倾向于在其中一方或另一方。在这张图中，蛋白质的分布并不是随机的；喜欢坐木筏的人聚在一起，喜欢出海的人也聚在一起。这非常吸引人，但它留下了一个重要的问题；为什么这些分子首先聚集成木筏和海洋？PI和合作者正在探索这样一种观点，即细胞壁的波动倾向于组织组成它的分子，就像海洋中的波浪影响漂浮在上面的海藻一样，在波峰时将它们分开，在波谷时将它们推到一起。

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.