Dramatic influence of patchy attractions on short-time protein diffusion under crowded conditions

In the dense and crowded environment of the cell cytoplasm, an individual protein feels the presence of and interacts with all surrounding proteins. While we expect this to strongly influence the short-time diffusion coefficient D_s of proteins on length scales comparable to the nearest-neighbor distance, this quantity is difficult to assess experimentally. We demonstrate that quantitative information about D_s can be obtained from quasi-elastic neutron scattering experiments using the neutron spin echo technique. We choose two well-characterized and highly stable eye lens proteins, bovine α-crystallin and γ_B-crystallin, and measure their diffusion at concentrations comparable to those present in the eye lens. While diffusion slows down with increasing concentration for both proteins, we find marked variations that are directly linked to subtle differences in their interaction potentials. A comparison with computer simulations shows that anisotropic and patchy interactions play an essential role in determining the local short-time dynamics. Hence, our study clearly demonstrates the enormous effect that weak attractions can have on the short-time diffusion of proteins at concentrations comparable to those in the cellular cytosol.