Cytoplasmic crowding acts as a porous medium reducing macromolecule diffusion

Destrian O, Moisan N, Mège RM, Ladoux B, Goyeau B, Chabanon M (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 123

Article Number: e2519599123

Journal Issue: 4

DOI: 10.1073/pnas.2519599123

Abstract

Intracellular transport of macromolecules is crucial for the proper functioning of most cellular processes. Although intracellular crowding is known to strongly alter macromolecule mobility, how cytoplasmic structures physically modulate diffusion remains largely unexplored. Here, we investigated the mechanisms by which cytoplasmic crowding controls diffusivity using live-cell experiments and porous media modeling approaches. Confocal microscopy combined with fluorescence recovery after photobleaching and fluorescence correlation spectroscopy measurements revealed an anticorrelation between free-green fluorescent protein diffusivity and the heterogeneous cytoplasmic structure abundance in live mammalian cells. This motivated the development of a multiscale model, where the cytoplasm is treated as a hierarchical porous medium with nanometric and micrometric obstacles. Numerically solving themodel allowed us to predict the effective cytoplasmic diffusion coefficient for various obstacle volume fractions, and to identify tortuous and porous hydrodynamic hindrances as key diffusion reduction mechanisms. Comparison with our experimental results highlighted the importance of hydrodynamic interactions between diffusing molecules and nanometric obstacles. Importantly, we found that the effective cytoplas-mic diffusivity was not dependent on specific intracellular regions but rather on the local intracellular obstacle volume fraction. Finally, the model was extended to predict the diffusivity of larger macromolecules, showing excellent agreement with literature data for several macromolecules and cell lines. This study provides insights into the physical mechanisms impeding intracellular diffusion, demonstrating the potential of porous media modeling approaches to predict transport mechanisms in dynamic or heterogeneous intracellular structures, as in cell motility, blebbing, and apoptosis.

Authors with CRIS profile

Benoit Ladoux

Involved external institutions

Laboratoire d'Énergétique Moléculaire et Macroscopique, Combustion (EM2C) FR France (FR) Institut Jacques Monod (IJM) FR France (FR)

How to cite

APA:

Destrian, O., Moisan, N., Mège, R.M., Ladoux, B., Goyeau, B., & Chabanon, M. (2026). Cytoplasmic crowding acts as a porous medium reducing macromolecule diffusion. Proceedings of the National Academy of Sciences of the United States of America, 123(4). https://doi.org/10.1073/pnas.2519599123

MLA:

Destrian, Olivier, et al. "Cytoplasmic crowding acts as a porous medium reducing macromolecule diffusion." Proceedings of the National Academy of Sciences of the United States of America 123.4 (2026).

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