Cytoplasmic crowding acts as a porous medium reducing macromolecule diffusion

Intracellular passive transport of macromolecules is crucial in many cellular functions, including cell motility, blebbing and apoptosis. Although intracellular crowding is known to strongly alter macromolecule mobility, how the presence of cytoplasmic structures physically modulates intracellular diffusion remains largely unexplored. Here we investigate the mechanisms by which cytoplasmic crowding controls diffusivity using a porous media modeling approach. 

We propose a multiscale diffusion model of the intracellular space inspired from up-scaling methods of transport in porous media. By treating the cytoplasm as a hierarchical porous medium with nanometric and micrometric obstacles, we are able to predict the effective cytoplasmic diffusion coefficient as a function of the obstacle volume fraction. We validate these results against experimental measurements of the effective diffusion coefficient in live cells by FRAP and FCS. These findings highlight the importance of two key diffusion reduction mechanisms: tortuosity and hydrodynamic drag. Importantly, we find that intracellular obstacle volume fraction is a master parameter controlling effective cytosolic diffusivity, independently on the cellular region. 

Altogether, this work demonstrates the potential of porous media modeling approaches to better understand transport phenomena in heterogeneous biological systems all the way to the intracellular scale.