Self Assembly of Biological Lipids and of Polymers

生物脂质和聚合物的自组装

• 批准号: 0140500
• 负责人: Michael Schick
• 金额: $ 27.9万
• 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: 2002
• 资助国家: 美国
• 起止时间: 2002-06-15 至 2006-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0140500&HistoricalAwards=false
• 关键词: Self; Assembly; Biological; Lipids; Polymers

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.***

这个理论项目将利用聚合物物理学的强大方法来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类的碳氢链是短链聚合物。其中一个问题就是对“木筏”的研究，“木筏”是磷脂海中的鞘脂和胆固醇的高密度岛屿；这些岛屿吸引了信号蛋白质等。尽管对这种现象有不同寻常的兴奋，因为它需要对膜的标准观点进行重大修订，但关于浮筏典型的不寻常的有序流体相几乎没有分子理论。这是一个相，其中的链比正常的液晶相具有较少的Guche键，但没有凝胶相的平移有序特征。包括自洽场理论在内的几种方法，以及对脂链的真实描述，将被用来理解鼓励或抑制RAFT形成的因素。第二个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。这一过程尚不清楚。该小组利用已被证明在聚合物研究中非常有用的模型对这一过程进行了模拟。这些模拟揭示了一种与通常接受的非常不同的融合机制。这些研究将继续，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。一般来说，这些重要蛋白质的结构尚不清楚，因为它们中的大多数还没有结晶，这是进行X射线分析的先决条件。最近，这种蛋白质的结晶是使用立方脂相完成的。为什么这种不寻常的阶段会产生蛋白质的晶体，这一点尚不清楚。这个问题与这个小组使用的技术非常吻合，他们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，可能会导致可以分析其结构的这种蛋白质的数量增加。这个理论项目将利用聚合物物理学的强大方法来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类的碳氢链是短链聚合物。所研究的项目展示了将聚合物物理方法应用于生物科学中的重要问题的巨大潜力。