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Research

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RESEARCH
Biophysics: Biological & Medical

Faculty in this area of research:

Applications of lasers to biology and medicine are pursued with studies in theoretical and experimental biological physics. Reflectance, fluorescence, and near-IR Raman spectroscopy are being used for biochemical/biophysical analysis of tissues and blood, and for diagnosis of dysplasia, cancer, Alzheimer's, atherosclerosis, and other diseases. A novel system for acquiring near-IR Raman spectra of microscopic samples has been developed and is being used for detailed studies of cancerous or otherwise diseased tissue of many organs. Clinical studies are being pursued with researchers from the Cleveland Clinic Foundation, Brigham and Women's Hospital, Metrowest Hospital, and New England Medical Center in colon, Barretts' esophagus, bladder, breast, coronary and peripheral arteries, and brain studies. Quantitative analysis of blood analytes through the skin using Raman spectroscopy is under development. UV resonance Raman spectroscopy is being explored to characterize dysplasia. A new technique based on observation of the nuclear signatures in reflectance spectra is being developed for measuring nuclear size distribution in biological tissues. Photon migration using a novel picosecond-pulse optical tomographic system is being used to image small fluorescent lesions imbedded in turbid biological tissue, and to study paths of early arriving photons. The mechanism of pulsed laser ablation of soft and hard biological tissues has been shown to be thermoelastic in origin. The experimental and theoretical work being conducted in this program is advancing new laser diagnostic technologies in the field of medicine.

The phase transition and aggregation of several biological molecules are studied. These phenomena are of great interest because the factors which govern phase separation and aggregation of biological molecules are believed to play a role in several human diseases such as cataracts, Alzheimer's disease, and cholesterol gallstones. A combination of experimental work, theoretical anaylysis, and computer simulations is used to understand how the interactions between such molecules govern their separation into coexisting phases.

Phase transitions and critical phenomena of gels are studied. Gels are a jello-like material made of a cross-linked network of polymers that contains a fluid. They undergo an abrupt change between collapsed and swollen states in response to a small change in temperature, solvent, acidity, light, electric field, or some molecules. The volume change is reversible and can be as large as many thousand times. The phase transition is universally found in synthetic and natural gels and is classified by four fundamental interactions: van der Waals, hydrophobic, electrostatic, and hydrogen bonding. Recent research involves theories and experiments on heteropolymers and heteropolymer gels in which monomers interact with different fundamental interactions. Heteropolymers are also a model for proteins. Theoretical analysis predicts that heteropolymers have four phases: swollen, collapsed and rubbery, frozen in a degenerate conformation, and frozen in a designed conformation. Experiments are under way to search for these phases and also to develop gels that can memorize conformation and recognize target molecules.

Heteropolymers composed of long, seemingly random, sequences of monomers, are ubiquitous in living matter. Understanding their global conformation, given the basic interactions between monomers, is a challenging problem of many-body physics. Focusing on the role of the long-range Coulomb interactions, theoretical studies reveal "necklace" phases composed of compact beads connected by stretched strands for charged heteropolymers and elevated freezing transitions for neutral heteropolymers. Polymer statistical mechanics is conducted by renormalization-group techniques. This method simultaneously yields both long-range properties, such as the scaling of end-to-end separation as a function of chain length, and local properties, such as the fraction of segmental bends. Thus, phase diagrams are obtained, exhibiting coil, rod, and globule phases. The approach is now being extended to heterogeneous systems and proteins.

The first steps in recognition of an image from the input to the eyes take place in the primary visual cortex (V1). Experiments have revealed that cells in V1 respond preferentially to inputs from one eye (ocular dominance) and to lines of particular direction (orientation preference). On the larger scale of the whole cortex, the patterns of response are organized into textures reminiscent of many two dimensional non-equilibrium motifs. Inspired by their similarity to quench patterns in symmetry-breaking phase transitions, Landau-Ginzburg equations are constructed for the evolution of macroscopic fields: Ocular dominance is represented by a scalar (Ising-like) order parameter, while orientation preference has a complex (XY-like) character. The natural defects in the two fields, domain walls and vortices respectively, are observed to repel each other. This requires a coupling between the two fields, which has a natural interpretation in the cortex's limited computational capacity.

The theory of chemotactic dynamics of bacteria has been developed and used to study pattern formation in bacterial colonies. The structures predicted by the mathematical model, such as travelling bands and rings, and collapsing aggregates, are observed in recent experiments on chemotactically interacting E. Coli.

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