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，而是显示出导致功能组织的物理组织，这一想法引起了极大的关注。这是因为这样的组织会影响许多生物学上重要的过程，如信号传导、内吞作用、膜融合和病毒进入等。尽管这一假说具有令人信服的性质，而且证据越来越多，但人们仍然对这一想法持怀疑态度。PI将研究一种机制，该机制源于质膜内外叶脂质组成的众所周知的变化。据推测，叶片之间的组成差异可能与膜的曲率有关，不饱和脂质偏好膜向外凸出的区域，而饱和脂质和胆固醇偏好膜向内凸出的相对叶片上的区域。众所周知，这种耦合原则上可以产生调制相位，例如显示交替条纹的相位。但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，具有其面积的特征在于弯曲模量与表面张力的比率的液滴。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，并使实验人员能够测试这种二维微乳液的存在。 该奖项支持理论研究和教育，以调查细胞壁中分子如何组织自己的物理机制。蛋白质是在我们的身体中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一起工作才能实现某些特定的功能。细胞壁一侧的蛋白质如何相互交流，它们又如何与细胞壁另一侧的蛋白质交流？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能找到彼此。而细胞壁一侧的蛋白质与另一侧的蛋白质相邻，这也是一个概率问题。最近有人提出，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筏子，这些分子有碳尾，像“不饱和脂肪”一样有双键。“细胞壁两侧的蛋白质被锚定在上面，这些锚可以区分木筏和大海，并且更喜欢在一个或另一个。因此，在这幅图中，蛋白质的分布不是随机的;那些喜欢木筏的蛋白质和那些喜欢大海的蛋白质靠得很近。这很吸引人，但它留下了一个重要的问题;为什么这些分子首先聚集成木筏和海洋？ PI和合作者正在探索这样一种想法，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，在波峰将它们分开，在波谷将它们推到一起。

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.