Cataract disease, the leading cause of blindness worldwide, is the end result of increased scattering of light within the human ocular lens. The proposed research continues to establish the multi-component phase diagram of concentrated, aqueous eye lens crystallin protein mixtures, together with its statistical-thermodynamic molecular basis. Neutron scattering, X-ray scattering, nuclear magnetic resonance, light scattering, statistical thermodynamic modeling, and computer simulation will be used to (1) test the prediction of non-monotonic dependence of alpha-gamma stability on interaction strength, and refine knowledge of the underlying molecular origins of the alpha-gamma phase diagram by testing ternary free energy models on available scattering data, (2) perform detailed experimental and theoretical investigation of orientation- dependent interactions between gamma crystallins, while focusing in part on screened, charge-regulated electrostatic interactions, and (3) systematically measure and analyze the phase diagrams and light scattering of controlled, quaternary aqueous mixtures of lens proteins, including the key alpha, beta, gamma, and buffer system. Each of these steps will involve the training of undergraduate researchers, who can be drawn from physics, chemistry, biology, mathematics, and computer science, and each step is an essential part of providing a sound molecular understanding of the light scattering, phase diagram, and dynamics of concentrated solutions and mixtures of gamma, alpha, and beta crystallin, and as such bears on the molecular origins of cataract.
Cataract disease, the leading cause of blindness worldwide, is the end result of increased scattering of light within the human ocular lens. This research seeks to contribute to the molecular basis of cataract, thereby taking needed steps toward the long-term goals of prevention and inhibition of this disease. Furthermore, the physical-chemical principles being investigated apply in a larger sense to many molecular features within living cells, and thus can facilitate much broader potential long-term benefits for human health.
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