Diffusion in protein solutions: the effect of crowding, temperature and charges

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We propose a research project on protein diffusion in solution as a function of the protein volume fraction, temperature, and importantly protein surface charge state. We will in particular focus on the dynamic effects of charge tuning and crowding. By adding suitable salts (both monovalent and multivalent) to the solutions, we can create different degrees of screening and also an inversion of the protein surface charge relevant for aggregation phenomena including crystallization. This charge-tuning has significant impact not only on the static (time-averaged) structure factor of the protein solutions, but also on their dynamics.In particular, dynamic density fluctuations may emerge through the formation of dynamic or transient protein clusters as a precursor of aggregation. It is expected that the lifetime of these dynamic clusters sensitively depends on the charge patterns. To explore these dynamic phenomena, we will systematically study the protein diffusion in these systems as a function of the charge state. The main experimental pathway will be to measure the incoherent scattering function of the protein solutions using neutron backscattering, to determine the short-time self-diffusion. Complementary information will be gained from neutron spin echo technique, dynamic light scattering, NMR and molecular dynamics simulations.