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联合资助。该项目将从理论上研究膜融合的过程，利用比以前更真实的人工膜和生物膜微观模型。PI打算同时应用解析自洽场理论和蒙特卡罗模拟，这一组合在过去已被证明是富有成效的。他最近的研究显示了一种新的核聚变途径，这与之前的预期不同。此外，他和他的合作者已经能够计算聚变过程中遇到的能量垒。他以前的研究是在仅由一种两亲体组成的平面双层膜上进行的。生物膜并非如此简单，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由几种成分组成的膜的研究。就像在生物膜中一样，它们将被限制在双分子层的一片或另一片叶子上。同样要研究的还有像细胞内那样的小球形囊泡。最后，融合肽的影响，这是目前的生物，对融合过程将建模。更广泛的影响预计这项工作将在技术应用和生物应用中应用于控制聚变事件。在前者中，人们可以引用聚合物囊泡的可能用途，其性质可以调整。为了使这些囊泡适当地运送它们的货物，融合事件是必要的。依赖于融合的生物过程的数量很多，但这里可以引用两个；HIV治疗中的融合控制及其在非病毒药物输送中的鼓励作用。这项工作将包括培养一名博士后研究员，并在随后的资助中培养一名学生。它将在全国会议和座谈会上传播，也将在PI针对大四学生和研究生的“生物物理学导论”课程的课堂上传播

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.***