SELF-ASSEMBLY AND SPONTANEOUS ORDER IN CROWDED SOLUTIONS

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Supramolecular biological structures are formed by the reversible association of amphiphilic molecules into extended aggregates. For example, the reversible self-assembly of cytoskeletal proteins into fiber bundles and networks constitutes the major determinant of the morphological and rheological properties of cells. In caricature, the pathological morphological and rheological properties of the red cells in sickle cell disease derive from the abnormal self-assembly of the mutant hemoglobin into long, thick "polymers'. These self-assembly processes occur in very crowded solutions where interactions between aggregates can lead to spontaneous orientational and positional ordering of the aggregates. Understanding these long-range effects of non-ideality is important for interpreting in vitro and in vivo observations. Statistical mechanical techniques from the field of complex fluids (including ones developed in-house) will be used to elucidate the behavior of both binary (single solute plus solvent) and ternary systems. For binary systems at equilibrium, the goals are to explain the ubiquitous positional ordering seen in micellar surfactant solutions, and to explore the effects of fiber flexibility on orientational ordering in solutions of reversibly "polymerizing" proteins. Studies of the kinetics of binary systems will analyze the effects of crowding on the progress of self-assembly and spatial ordering. For hemoglobin ternary systems, the goals are to understand how non-sickle hemoglobins affect the behavior of sickle cell hemoglobin in heterozygous and double heterozygous individuals. For cytoskeletal ternary systems, studies will explore the effect of interactions between different cytoskeletal fibers and the various ways that the reversible binding of cytoskeletal accessory proteins can influence cytoskeletal structure, both in-homogeneous solutions and with imposed spatial gradients. By elucidating the molecular determinants of the highly cooperative behavior of self-assembling structures under crowded conditions, we hope to be able to identify important points of normal and pathological control, and contribute to an improved framework for therapeutic strategies.