Towards a Description of Fusion In More Realistic Models of Membranes

该基金由材料研究部和分子与细胞生物科学部共同资助。智力成果该项目将利用比以前更真实的人工和生物膜的微观模型，从理论上研究膜融合的过程。 PI打算同时应用解析自洽场理论和蒙特卡罗模拟，这在过去已经证明是富有成效的组合。他最近的研究显示了一种新的融合途径，与以前预期的不同。此外，他和他的合作者已经能够计算融合过程中遇到的能量障碍。他以前的研究是在由单一两亲物组成的平面双层膜上进行的。生物膜并不那么简单，因此他的目标是确定现实膜的各种因素特征如何影响融合过程。 他将把他的方法应用于研究几种成分的膜。在生物膜中，它们将被限制在双层的一个叶子或另一个。也要研究的是像细胞内的小球形囊泡。最后的影响fusionpeptides，这是目前的生物，融合过程中将model.broader ImpactsIt预计，这项工作将有应用程序控制融合事件，无论是在技术应用和生物的。在前者中，可以列举其性质可以调节的聚合物囊泡的可能用途。融合事件是必要的，以便这些囊泡适当地提供其货物。依赖于融合的生物学过程的数量很多，但这里可以引用两个：HIV治疗中融合的控制，以及它在非病毒药物递送中的鼓励。 这项工作将包括培训一名博士后研究员，并在以后的赠款中培训一名学生。它将在国家会议和学术讨论会上传播，并将在PI的“生物物理学入门”课程中传播，该课程针对的是高年级学生和研究生。

This grant is funded jointly by the Division of Materials Research and the Division of Molecular and Cellular Biosciences.Intellectual MeritThe project will study theoretically the process of membrane fusion utilizing more realistic microscopic models of both artificial and biological membranes than employed previously. The PI intends to apply both analytic self-consistent field theory and Monte Carlo simulation, a combination which has proved fruitful in the past. His recent studies have shown a new pathway for fusion which is different from that previously expected. Further, he and his collaborators have been able to calculate the energy barriers encountered in the fusion process.His previous studies were carried out on planar bilayer membranes consisting of but a single amphiphile. Biological membranes are not so simple, and so his objective is to determine how various factors characteristic of realistic membranes affect the fusion process. He will apply his methods to the study of membranes with several components. As in biological membranes, they will be restricted to one leaf of the bilayer or the other. Also to be studied are small spherical vesicles like those within the cell. Finally the effects of fusionpeptides, which are present biologically, on the fusion process will be modeled.Broader ImpactsIt is expected that the work will have application to controlling fusion events, both in technological applications and in biological ones. Among the former, one can cite the possible use of polymeric vesicles whose properties can be tuned. Fusion events are necessary in order that these vesicles deliver their cargoes appropriately. The number of biological processes dependent upon fusion are legion, but two can be cited here; control of fusion in HIV therapy, and its encouragement in non-viral drug delivery. The work will involve the training of a post-doctoral fellow and, later in the grant, a student. It will be disseminated at national meetings and colloquia, and also in the classroom in the PI's course "Introduction to Biological Physics" which is aimed at seniors and graduate students.***