MICROSTRUCTURAL HETEROGENEITY IN MEMBRANES

描述（改编自申请人的摘要）：本项目的长期目标 该项目的目的是定义细胞所需的脂质分子排列 膜融合。 重点是了解分子细节 模型脂质膜与聚乙二醇介导的融合 [聚乙二醇]。 获得的信息将促进 PEG 介导的细胞融合 技术并提供有关蛋白质如何介导细胞融合的见解 膜。 PEG 通过去除水而使模型膜紧密接触 他们之间。 脂质的生物分子小叶组织成封闭的 囊泡结构充当细胞膜的模型。 伦茨集团 已经表明，接触单层中的分子堆积被破坏 脂质双层会诱导膜融合。 接下来的时间进程 融合过程也已被定义并被证明具有显着的相似性 病毒膜融合和分泌中观察到的事件顺序 颗粒融合，除了更多的分子细节可以定义在 伦茨小组进行的模型膜实验。 伦茨博士现在计划定义分子细节，因为它们发生在融合中 PEG聚集模型膜并比较模型膜过程 利用有关生物膜融合的已知信息来检验假设 这两个过程共享分子机制。 这将涉及到 三个具体目标：1]定义并比较模型的动力学和 生物膜融合； 2]定义发生的脂质结构重排 融合期间； 3]确定膜结构扰动如何影响 改变融合过程。 此外，Lentz博士将测试肽是否 脂鞘病毒融合蛋白的片段（在这种情况下， 流感；其他包括人类和猿猴免疫缺陷病毒）将 以增强膜融合的方式破坏双层。 三个具体目标 此处还将讨论：1]定义病毒融合肽的作用 模型膜及其 PEG 介导的融合； 2]测试是否脂质 堆积破坏对于让肽与膜结合至关重要 融合诱导构象； 3]确定流感病毒如何 融合肽可能会改变膜结构，从而促进更多的一种 融合过程中的步骤。

DESCRIPTION (Adapted from applicant's abstract): The long term goal of this project is to define the lipid molecule arrangements necessary for cell membrane fusion. The focus is on understanding the molecular details of the fusion of model lipid membranes with as mediated by poly(ethylene glycol) [PEG]. The information obtained will advance PEG-mediated cell fusion technologies and provide insight into how proteins mediate fusion of cell membranes. PEG acts to bring model membranes into close contact by removing the water between them. Biomolecular leaflets of lipids organized into closed vesicular structures serve as models for cell membranes. The Lentz group has shown that disrupted molecular packing in the contacting monolayers of lipid bilayers will induce membrane fusion. The time course of the ensuing fusion process has also been defined and shown to bear remarkable similarity to the sequence of events observed in viral membrane fusion and secretory granule fusion, except that many more molecular details can be defined in the model membrane experiments carried out by the Lentz group. Dr. Lentz plans now to define molecular details as they occur in fusion of PEG-aggregated model membranes and to compare the model membrane process with what is known about biomembrane fusion in order to test the hypothesis that these two processes share molecular mechanisms. This will involve three specific aims: 1] define and compare the kinetics of model and biomembrane fusion; 2] define the lipid structural rearrangements that occur during fusion; and 3] determine how membrane structural perturbations might alter the fusion process. In addition, Dr. Lentz will test whether peptide fragments from the fusion proteins of lipid-sheathed viruses (in this case, influenza; others include human and simian immunodeficiency virus) will disrupt bilayers in ways that enhance membrane fusion. Three specific aims will also be addressed here: 1] define the effects of viral fusion peptide on model membranes and on their PEG-mediated fusion; 2] test whether lipid packing disruption is critical to allow peptide to bind to membranes in a fusion-inducing conformation; and 3] determine how the influenza viral fusion peptide might alter membrane structure so as to encourage one of more steps in the fusion process.