This multifaceted project aims at understanding the physical basis for various cell activities that involve structural changes in supramolecular biomolecular complexes. Recent emphasis has been on mechanisms involved in biological vesicle formation, but several projects involving tubulin polymers also were carried out. A thermodynamic analysis of protein coat assembly in receptor mediated endocytosis was used to establish relationships between clathrin basket assembly and parameters such as clathrin interarm association energies, intrinsic triskelion curvature, and the bending rigidity of the triskelions. Fluorescence recovery after photobleaching (FRAP) was employed to study temperature induced structural changes in bilayers formed from total lipid extracts of E.coli cell membranes, the purpose being to understand phase changes that occur when cellular lipids are maintained at temperatures near their growth temperatures. A series of physical analyses involving dynamic light scattering and small angle neutron scattering were undertaken to determine parameters of microtubule structure, particularly as they are affected by a variety of antimitotic drugs; in particular, protocols were devised for using quasielastic light scattering to study the induction of tubulin rings by marine natural peptides, such as cryptophycin and dolastatin, which are being investigated as potential new chemotherapeutic agents. - biological vesicles, endocytosis, clathrin, FRAP, dynamic light scattering, SANS, tubulin

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Intramural Research (Z01)
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Special Emphasis Panel (LIMB)
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Galanis, Jennifer; Nossal, Ralph; Harries, Daniel (2010) Depletion forces drive polymer-like self-assembly in vibrofluidized granular materials. Soft Matter 6:1026-1034
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Svitel, Juraj; Boukari, Hacene; Van Ryk, Donald et al. (2007) Probing the functional heterogeneity of surface binding sites by analysis of experimental binding traces and the effect of mass transport limitation. Biophys J 92:1742-58
Michelman-Ribeiro, Ariel; Horkay, Ferenc; Nossal, Ralph et al. (2007) Probe diffusion in aqueous poly(vinyl alcohol) solutions studied by fluorescence correlation spectroscopy. Biomacromolecules 8:1595-600
Michelman-Ribeiro, Ariel; Nossal, Ralph; Morris, Ryan et al. (2006) Electrolysis induces gradients and domain orientation in agarose gels. Phys Rev E Stat Nonlin Soft Matter Phys 73:011410
Barr, Valarie A; Balagopalan, Lakshmi; Barda-Saad, Mira et al. (2006) T-cell antigen receptor-induced signaling complexes: internalization via a cholesterol-dependent endocytic pathway. Traffic 7:1143-62
Ferguson, Matthew L; Prasad, Kondury; Sackett, Dan L et al. (2006) Conformation of a clathrin triskelion in solution. Biochemistry 45:5916-22
Jin, Albert J; Prasad, Kondury; Smith, Paul D et al. (2006) Measuring the elasticity of clathrin-coated vesicles via atomic force microscopy. Biophys J 90:3333-44
Skupsky, R; Losert, W; Nossal, R J (2005) Distinguishing modes of eukaryotic gradient sensing. Biophys J 89:2806-23

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