Biomolecule transport across biomembranes in the presence of crowding: polymer translocation driven by concentration and disorder gradients.

The transport of biomolecules across biomembranes occurs in a complex environment where the fluid on both sides of the membrane contains many inclusions. We investigate the translocation of a polymer through a nanopore in such crowded environments via computer simulations. Modeling intracellular and extracellular inclusions as spherical obstacles, the emergence of an entropic driving force is demonstrated for (i) a gradient in the number of obstacles on either side of the pore and (ii) having the obstacles in an ordered arrangement on one side and disordered on the other. With a directional preference of ≈90% of events occurring towards the disordered side and a reduction in the translocation time of ≈30%, the latter case represents a manifestation of entropic trapping. Simple estimates for the magnitude of the driving force are developed for both cases. The effect of allowing the obstacles to move as well as systems containing opposing concentration and disorder gradients are also explored. Demonstrating a robust conclusion that translocation to lower obstacle densities and higher degrees of disorder will be accelerated, these results suggest that accounting for such effects will be critical in developing a realistic model of in vivo translocation.