Peter Debye Institute for Soft Matter Physics, University Leipzig, Linnéstraße 5, 04103, Leipzig, Germany.
Fraunhofer Institute for Cell Therapy and Immunology, Perlickstraße 1, 04103, Leipzig, Germany.
Adv Mater. 2021 Jul;33(29):e2101840. doi: 10.1002/adma.202101840. Epub 2021 Jun 3.
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 (D O) and its stronger hydrogen bonds. Adding D O 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 D O, 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. D O 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.
溶剂条件出人意料地充足,可以极大地、可逆地减缓细胞的速度。在体外的分子水平上,在重水(D2O)及其更强氢键的存在下,蛋白质-溶剂相互作用会发生剧烈变化。向活细胞的细胞培养基中添加 D2O 会增加分子细胞内的粘度。虽然细胞形态和表型保持不变,但细胞动力学以可变化的方式转变为慢动作。这表现在细胞增殖和迁移的减缓上,这是由于细胞质的可逆胶凝作用引起的。类似于时间-温度超叠加原理,其中温度被 D2O 取代,粘度的增加会减缓有效时间。细胞质中至关重要的结构肌动蛋白网络从幂律型粘弹性转变为更具橡胶弹性的行为。由此产生的细胞内阻力和耗散会损害细胞运动。由于细胞是高度适应的非平衡系统,从热力学角度来看,它们通常会不可逆地做出反应。然而,D2O 诱导的变化是完全可逆的,其影响与信号转导以及表达无关。更强的氢键导致类似玻璃的、拉长的分子内动力学,这可能有助于更长时间地储存生物物质,例如在器官移植的运输过程中。