Physical and mathematical methods are used to solve problems in the biomedical sciences, with emphasis on describing properties of biological materials and understanding phenomena in cell physiology. Special attention is being given to determining physical properties of structures formed from clathrin triskelions, the latter being large three-arm protein complexes that are involved in a major process by which eucaryotic cells take up materials from the extracellular milieu (receptormediated endocytosis). To gain insight into related energetic aspects of the endocytotic process, we developed a set of novel analytical and computational tools that relate shape variations in triskelions to underlying mechanical properties of the molecules. Foremost among these are statistical methods used to quantitate information obtained from electron micrographs of clathrin triskelions. By analyzing the fluctuations about the average shape profile, we determined that the bending rigidity is approximately constant along the triskelion backbone, and that the rigidity of a lattice patch is equivalent to, and perhaps three times higher than, that of an equivalent area of plasma membrane. Hence, any detailed analysis of the budding of clathrin-coated vesicles from cell surfaces during receptor-mediated endocytosis must consider properties of both the clathrin and the membrane. To obtain relevent thermodynamic or energetic parameters, we have been using dynamic light scattering to directly assess the phase-space characteristics of the clathrin assembly process. Other projects include a mathematical analysis of data on the ligand-induced stiffening of neutrophils, and light and neutron scattering studies of structural transformations induced in microtubule arrays and agarose gels by chemical and electrical stimuli.
