Protein Diffusion in crowded solutions and biological cells

Wolfgang Doster, Technical University, Munich

The cytoplasm of red blood cells is densely packed with hemoglobin molecules at a volume fraction of 0.25 and thus represents a congested solution. The self-diffusion coefficient of hemoglobin is about six times lower than the value measured in dilute solution. In contrast, the collective or gradient diffusion coefficient is only slightly reduced. According to the established view, protein diffusion in congested media is obstructed by excluded volume interactions. Combining neutron spin-echo and back-scattering spectroscopy with low angle scattering experiments, protein diffusion is analysed on the scale of the inter-molecular distance: The decay of the dynamical structure factor is heterogeneous in time due to memory effects. The effective diffusion coefficient decreases with the wave-vector or with decreasing length scale indicating a cross-over of self- and collective diffusion. Moreover, a wave-vector dependent friction function is derived, which is a characteristic feature of hydrodynamic interactions. The wave-vector and concentration dependence of the long-time self-diffusion coefficient of hemoglobin in solution and in red blood cells agree qualitatively with theoretical predictions on the diffusion in hard spheres. To obtain quantitative agreement however, the volume fraction had to be renormalized. The effective protein volume fraction may thus include part of the hydration shell because of a larger surface to volume ratio compared to standard colloids of much larger size.

Lit. W. Doster and S. Longeville Biophys.J. (2007) 93:1360.

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