Quantitative physical and mathematical methods have been applied to several research problems in cell biophysics and tissue optics. In cell biophysics, recent emphasis has been on determining the mechanical and structural properties of large (mesoscopic) molecular structures. Particular attention is being given to the lattice rearrangements that occur when a network of clathrin triskelions initially located on a cell surface (a """"""""coated pit"""""""") buds off to form a basket (""""""""coated vesicle""""""""). We developed a set of novel analytical and computational tools to relate the shape variations of triskelions to the underlying mechanical properties of the molecules. These methods are being used to obtain from electron micrographs quantitative information regarding the flexibility of the triskelion arms and the mechanical properties of the central hub where the arms are joined. The mesoscopic structure of macromolecular complexes are also being probed by diffraction measurements utilizing neutrons or light. During the past year, we continued our studies of agarose gels, which serve as models for various biopolymer matrices. Recent emphasis has been on understanding how solution properties affect network junctions, and how gel structure is changed by applied electric fields. Electric field effects are only weakly apparent on the length scales probed by neutrons, and to extend the range of observation, a collaborative study of small angle light scattering has been initiated with investigators at Boston University. In our investigations of the theory and practice of tissue optics, we devised an optically-based noninvasive method to quantity thermal damage in tissue. That method was used to study thermal lesions induced in bovine myocardium in vitro. Algorithms, based on a photon random walk treatment of light diffusion, were developed to provide optical coefficients from the measured transmittances and reflectances. In collaboration with investigators from the National Cancer Institute, we are presently using similar methods to characterize the optical properties of human breast tissues. In a related project, we performed a theoretical analysis of resolution limits for time-resolved imaging of tumors in human breast. Photon migration theory was used to predict the spatial resolution of objects embedded at different depths within a finite slab, and dependencies on scattering cross section, sample thickness, and photon transmit time were determined.
