MICROSTRUCTURAL HETEROGENEITY IN MEMBRANES

膜的微观结构异质性

• 批准号: 2900583
• 负责人: Barry R Lentz
• 金额: $ 24.87万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-12-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2900583
• 关键词: Orthomyxoviridae; chemical kinetics; chimeric proteins; fluorescent dye /probe; hemagglutinin; lipid bilayer membrane; lipid structure; liposomes; membrane fusion; membrane lipids; membrane structure; molecular polarity; phosphatidylcholines; phosphatidylserines; polyethylene glycols; thermodynamics; virus protein

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.

描述（改编自申请人的摘要）：本项目的长期目标 该项目旨在确定细胞所需的脂质分子排列， 膜融合 重点是了解分子的细节， 聚乙二醇介导的模型脂膜与AS的融合 [PEG]。 所获得的信息将促进PEG介导的细胞融合 技术，并提供深入了解蛋白质如何介导细胞融合 膜。 PEG的作用是通过除去水使模型膜紧密接触 他们之间 脂质的生物分子小叶组织成闭合的 泡状结构作为细胞膜的模型。 Lentz集团 已经表明，在接触单层中的破坏的分子堆积 脂质双层将诱导膜融合。 接下来的时间进程 熔合过程也被定义，并显示出具有显著的相似性 在病毒膜融合和分泌中观察到的事件序列 颗粒融合，除了更多的分子细节可以定义在 Lentz小组进行的模型膜实验。 博士Lentz现在计划定义分子细节，因为它们发生在融合过程中。 PEG-聚集模型膜，并比较模型膜过程 与已知的生物膜融合来验证这个假设 这两个过程共享分子机制。 这将涉及 三个具体目标：1]定义和比较模型的动力学， 生物膜融合; 2]定义发生的脂质结构重排 在融合过程中;和3]确定膜结构扰动如何可能 改变聚变过程 此外，伦茨博士将测试肽是否 来自脂质鞘病毒的融合蛋白的片段（在这种情况下， 流感;其他包括人类和猿免疫缺陷病毒）将 以增强膜融合的方式破坏双层。 三个具体目标 本文还将讨论：1]定义病毒融合肽的作用 在模型膜上和在它们的PEG介导的融合上; 2]测试脂质 包装破坏对于允许肽结合到膜上是至关重要的， 融合诱导构象;和3]确定流感病毒如何 融合肽可能会改变膜结构，以促进一种或多种细胞的生长 融合过程中的步骤。