Towards a Description of Fusion In More Realistic Models of Membranes

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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.***