9732083 Siggia This grant is funded jointly by the Divisions of Materials Research, Physics, and Molecular and Cellular Biology. Phenomenological methods developed in condensed matter physics will be applied to problems in cell biology ranging from the mechanics of biomolecules to the formation of organelles. In contrast to approaches taken by cell biologists, for selected problems physical theory can make semiquantitative predictions before the biochemistry is known, and connect models to experiments in ways biologists cannot. Quantitative force-distance measurements of DNA interacting with condensing agents (histones and polyamines) will be modeled in order to extract binding agents, protein-protein interactions and the kinetics of association. General questions about folding pathways in RNA and its behavior when mechanically extended will be investigated by a kinetic Monte Carlo code for the secondary structure, including `pseudo-knots.' Classical studies of chromosomes in meiotic prophase strongly suggest the morphology of a polymer brush. Polymer theory then explains a number of their properties that were otherwise mysterious and makes semiquantitative predictions about forces and tensions which are feasible to check experimentally. The biases that cause topoisomerase II to resolve the engangled sister chromatid arms during mitosis may be understood in terms of a multiphase polymer blend. Collaborations will continue with the laboratory of Lippincott- Schwartz at NIH including work on the quantitative analysis of photobleach experiments; testing whether data for the drug induced dissolution of the Golgi is compatible with an interorganelle surface tension driven flow; and, develop and test physical-chemical models for the organization of the Golgi and other steps in protein secretion. A kinetic Monte Carlo or molecular dynamics code will be developed for short polymers consisting of hydrophobic and hydrophilic monomers and will be used to simul ate dynamical processes in bilayer membranes such as fusion and budding. Realistic numbers of lipids and almost reasonable times can be attained this way. Similar generic and coarse grained models for the proteins that catalyze fusion can be included, and the simulations then are a heuristic tool from which to develop a simple physical picture as to how proteins destabilize the bilayer. An effort will be made also to extend prior calculations of anomalous scaling in passive scaler advection to the velocity field. At present there are no deductive theories as to why velocity fluctuations become increasingly non-Gaussian as the scale size increases. %%% This grant is funded jointly by the Divisions of Materials Research, Physics, and Molecular and Cellular Biology. Phenomenological methods developed in condensed matter physics will be applied to problems in cell biology ranging from the mechanics of biomolecules to the formation of organelles. In contrast to approaches taken by cell biologists, for selected problems physical theory can make semiquantitative predictions before the biochemistry is known, and connect models to experiments in ways biologists cannot. ***
