Quantitative assessment of the spatial crowding heterogeneity in cellular fluids

Mammalian cells are crowded with macromolecules, supramolecular complexes, and organelles, all of which equip intracellular fluids, e.g., the cytoplasm, with a dynamic and spatially heterogeneous occupied volume fraction. Diffusion in such fluids has been reported to be heterogeneous, i.e., even individual single-particle trajectories feature spatiotemporally varying transport characteristics. Complementing diffusion-based experiments, we have used here an imaging approach to assess the spatial heterogeneity of the nucleoplasm and the cytoplasm in living interphase cells. As a result, we find that the cytoplasm is more crowded and more heterogeneous than the nucleoplasm on several length scales. This phenomenon even persists in dividing cells, where the mitotic spindle region and its periphery form a contiguous fluid but remain nucleoplasmlike and cytoplasmlike, respectively.