Starvation induces diffusion hindrance at the nanoscale in mammalian cells

Prolonged starvation leads to acute stress, inducing a state of cellular dormancy with reduced energy consumption. Our research reveals that nutrient deprivation halts the movement of large ribosomal subunits, trapping them in a gel-like structure within the cytoplasm of surviving cells. This effect is due to water efflux from cells, causing a decrease in cell volume to half the original volume. This simple physical strategy saves, in a dormant state 10 7 ATP per second, which is needed for normal protein production. We monitored the diffusion of GFP (radius 2.3 nm) and 40S and 60S ribosomes (radii 3.75 and 15 nm, respectively) in the cytoplasm and nucleus during starvation of HeLa cells. GFP and 40S ribosomes slowed their diffusion in the cytoplasm two and five times, respectively. 60S ribosomes exhibited only rotational diffusion. In non-starving cells, biomolecules get stuck in the gel structure of cytoplasm with sizes >100 nm. We show that the gel pore size decreased from 100 nm to 30 nm upon starvation. The diffusive transport in the cell nucleus didn't change during starvation. GFP and ribosomes had the same diffusion coefficients in non-starving and starving cells in the nucleus. This highlights the importance of nuclear transport in cancer cells during extreme stress conditions. Prolonged starvation leads to intracellular diffusion hindrance, inducing a state of cellular dormancy with reduced energy consumption.