Self Assembly of Biological Lipids and of Polymers

这个理论项目将利用高分子物理学的强大方法研究几个重要的生物学问题。 这是可能的，因为构成体内所有膜的生物脂质的烃链是短链聚合物。 其中一个问题是研究“筏”，即磷脂海中鞘脂和胆固醇的高密度岛屿;岛屿吸引信号蛋白等。 虽然有不寻常的兴奋有关这一现象，因为它需要重大修订的标准观点的膜，有很少的分子理论上的不寻常的有序流体相典型的筏。 这是其中链具有比正常液晶相更少的交错键的相，但没有凝胶相的平移顺序特征。 几种方法，包括自洽场理论，将沿着脂链的现实描述来理解促进或抑制筏形成的因素。第二个非常重要的问题是膜融合，这是病毒感染、受精和大多数细胞内运输所必需的过程。 这个过程不被理解。 该小组利用模型对这一过程进行了模拟，这些模型已被证明在聚合物研究中有很大的用途。 这些模拟揭示了一个非常不同的融合机制比通常接受。 这些研究将继续进行，以阐明融合过程中遵循的途径。 考虑到融合和感染以及融合和受精之间的联系，潜在的影响是巨大的。 另一个值得注意的项目是关于膜蛋白结晶的研究。 这些重要的蛋白质的结构是未知的，一般来说，因为它们中的大多数还没有被结晶，这是X射线分析的先决条件。 而最近，这种蛋白质的结晶是使用立方脂质相完成的。 为什么这些不寻常的阶段会导致蛋白质晶体的产生还不清楚。 这个问题很好地符合这个小组所使用的技术，该技术成功地预测了嵌段共聚物中各种双连续立方相的存在和不存在，并将这些技术扩展到包括脂质膜和蛋白质之间的相互作用。 如果能够理解这一过程的基本原理，就可能导致可以分析结构的此类蛋白质数量的增加。%这个理论项目将利用高分子物理学的强大方法研究几个重要的生物学问题。 这是可能的，因为构成体内所有膜的生物脂质的烃链是短链聚合物。 所研究的项目说明了将聚合物物理学方法应用于生物科学中重要问题的巨大潜力。

This theoretical project will study several important biological problems utilizing powerful methods from polymer physics. This is possible because the hydrocarbon chains of biological lipids, which make up all membranes within the body, are short chain polymers. One such problem is the study of "rafts," high density islands of sphingolipids and cholesterol in the phospholipid sea; islands which attract, inter alia, signalling proteins. Although there is unusual excitement about this phenomena, as it requires significant revision of the standard view of membranes, there is little molecular theory on the unusual ordered fluid phase typical of the raft. This is a phase in which the chains have fewer gauche bonds than the normal liquid crystal phase, yet is without the translational order characteristic of the gel phase. Several methods, including self-consistent field theory, will be utilized along with a realistic description of the lipid chains to understand the factors which encourage, or inhibit, the formation of rafts.A second problem of great importance is that of membrane fusion, a process necessary for viral infection, fertilization, and most intra-cell trafficking. The process is not understood. This group has carried out simulations of this process utilizing models which have proved of great use in the study of polymers. These simulations reveal a very different fusion mechanism than that commonly accepted. These studies will continue in order to elucidate the pathway which is followed during fusion. The potential impact is great given the connection between fusion and infection, and fusion and fertilization. Another project of note is that concerning the study of crystallization of membrane proteins. The structure of these important proteins is not known, in general, as most of them have not been crystallized, a prerequesite for x-ray analysis. Rather recently crystallization of such proteins was accomplished using cubic lipid phases. Why such unusual phases should bring about crystals of proteins is not understood. This problem fits well with the techniques used by this group, which successfully predicted the existence, and non-existence, of various bicontinuous cubic phases in block copoloymers, and have extended these techniques to include interaction between lipid membranes and proteins. If the basic principles underlying this process can be understood, it could lead to an increase in the number of such proteins whose structure can be analyzed.%%%This theoretical project will study several important biological problems utilizing powerful methods from polymer physics. This is possible because the hydrocarbon chains of biological lipids, which make up all membranes within the body, are short chain polymers. The projects studied illustrate the great potential of bringing methods of polymer physics to bear upon important problems in the biological sciences.***