Rodenfels2019 - Heat Oscillations Driven by the Embryonic Cell Cycle Reveal the Energetic Costs of Signaling

All living systems function out of equilibrium and exchange energy in the form of heat with their environment. Thus, heat flow can inform on the energetic costs of cellular processes, which are largely unknown. Here, we have repurposed an isothermal calorimeter to measure heat flow between developing zebrafish embryos and the surrounding medium. Heat flow increased over time with cell number. Unexpectedly, a prominent oscillatory component of the heat flow, with periods matching the synchronous early reductive cleavage divisions, persisted even when DNA synthesis and mitosis were blocked by inhibitors. Instead, the heat flow oscillations were driven by the phosphorylation and dephosphorylation reactions catalyzed by the cell-cycle oscillator, the biochemical network controlling mitotic entry and exit. We propose that the high energetic cost of cell-cycle signaling reflects the significant thermodynamic burden of imposing accurate and robust timing on cell proliferation during development.

所有生命系统均以非平衡态运行，并以热量形式与外界环境进行能量交换。由此，热流可用于反映细胞进程的能量消耗——而这类消耗在很大程度上仍未被充分认知。本研究对一台等温量热仪（isothermal calorimeter）进行改装，用以测量发育中的斑马鱼胚胎（zebrafish embryos）与其周围培养基之间的热流。热流随时间推移随细胞数量增多而升高。令人意外的是，热流存在显著的振荡组分，其周期与同步化的早期还原性卵裂相匹配；即便通过抑制剂阻断DNA合成与有丝分裂过程，该振荡现象仍持续存在。进一步机制分析表明，热流振荡实则由细胞周期振荡器（cell-cycle oscillator）所催化的磷酸化与去磷酸化反应驱动——该生物化学网络负责调控有丝分裂的启动与退出。我们提出，细胞周期信号传导的高能量消耗，反映了在发育过程中为细胞增殖赋予精准且稳定的时序所带来的显著热力学负担。