Protein motion in the dense and crowded environment of a living cell is essential for the functioning of the cellular machinery. In particular, the so-called short time diffusion on small length scales comparable to the typical distance between two proteins is a key quantity for many processes such as signal transmission or reactions between proteins, but has remained extremely difficult to determine experimentally under conditions prevailing in cells.
Scientists at the Division of Physical Chemistry at Lund University and Forschungszentrum Jülich (Germany) have now used neutron scattering experiments combined with computer simulations to study diffusion in such crowded protein solutions. While they show that diffusion is slowed down in general as protein concentration increases, this decelerating effect is dramatically amplified when interactions become weakly attractive as is frequently the case between many proteins. A particularly large effect can be attributed to weakly attractive patchy, i.e. anisotropic interactions, where a decrease of the local short time diffusion under crowded conditions by almost 3 orders of magnitude compared to the dilute case can be found. Their study thus points out that traditional in vitro experiments under dilute conditions may completely fail when trying to mimic and understand cellular processes, and demonstrate the potential of neutron scattering based techniques combined with advanced simulations in attempts to gain insight into protein diffusion in a living cell. The work has been published in Science Advances.