MICROSTRUCTURAL HETEROGENEITY IN MEMBRANES

描述(改编自申请人的摘要)：该项目的长期目标 项目是定义细胞所需的脂类分子排列 膜融合。重点是了解细胞的分子细节 聚乙二醇介导型AS与模型脂膜的融合 [钉住]。所获得的信息将促进聚乙二醇介导的细胞融合 技术，并深入了解蛋白质如何介导细胞融合 膜。 聚乙二醇酯通过去除水使模型膜紧密接触。 在他们之间。组织成闭合的脂类生物分子小叶 泡状结构可作为细胞膜的模型。Lentz集团 已经表明，在接触的单分子层中破坏了分子堆积 脂质双分子层可诱导膜融合。随之而来的时间进程 核聚变过程也被定义并显示出惊人的相似性 对病毒膜融合和分泌过程中观察到的事件顺序的影响 颗粒融合，除了更多的分子细节可以在 模型膜实验由Lentz小组进行。 Lentz博士现在计划定义分子细节，因为它们发生在 聚乙二醇聚集体模型膜与模型膜过程的比较 已知的生物膜融合以检验这一假说 这两个过程具有共同的分子机制。这将涉及到 三个具体目标：1)定义并比较模型和 生物膜融合；2]定义发生的脂类结构重排 在融合过程中；以及3]确定膜结构扰动如何 改变核聚变过程。此外，伦茨博士还将测试多肽是否 来自脂膜病毒融合蛋白的片段(在这种情况下， 流感；其他包括人类和猿类免疫缺陷病毒)将 以增强膜融合的方式破坏双分子层。三个具体目标 还将在这里讨论：1]定义病毒融合肽的作用 在模型膜和它们的聚乙二醇介导的融合上；2]测试脂类 包装破坏是使多肽与膜结合在一起的关键 融合诱导构象；以及3]决定流感病毒如何 融合肽可能会改变膜结构，从而促进一种或多种 融合过程中的几个步骤。

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.