Cells in Slow Motion: Apparent Undercooling Increases Glassy Behavior at Physiological Temperatures

Abstract Solvent conditions are unexpectedly sufficient to drastically and reversibly slow down cells. In vitro on the molecular level, protein–solvent interactions drastically change in the presence of heavy water (D₂O) and its stronger hydrogen bonds. Adding D₂O to the cell medium of living cells increases the molecular intracellular viscosity. While cell morphology and phenotype remain unchanged, cellular dynamics transform into slow motion in a changeable manner. This is exemplified in the slowdown of cell proliferation and migration, which is caused by a reversible gelation of the cytoplasm. In analogy to the time–temperature superposition principle, where temperature is replaced by D₂O, an increase in viscosity slows down the effective time. Actin networks, crucial structures in the cytoplasm, switch from a power‐law‐like viscoelastic to a more rubber‐like elastic behavior. The resulting intracellular resistance and dissipation impair cell movement. Since cells are highly adaptive non‐equilibrium systems, they usually respond irreversibly from a thermodynamic perspective. D₂O induced changes, however, are fully reversible and their effects are independent of signaling as well as expression. The stronger hydrogen bonds lead to glass‐like, drawn‐out intramolecular dynamics, which may facilitate longer storage times of biological matter, for instance, during transport of organ transplants.