Center of Molecular Immunology, Havana, Cuba.
Cancer Research UK Beatson Institute, Glasgow, UK.
Sci Rep. 2018 May 29;8(1):8349. doi: 10.1038/s41598-018-26724-7.
Cell metabolism is characterized by three fundamental energy demands: to sustain cell maintenance, to trigger aerobic fermentation and to achieve maximum metabolic rate. The transition to aerobic fermentation and the maximum metabolic rate are currently understood based on enzymatic cost constraints. Yet, we are lacking a theory explaining the maintenance energy demand. Here we report a physical model of cell metabolism that explains the origin of these three energy scales. Our key hypothesis is that the maintenance energy demand is rooted on the energy expended by molecular motors to fluidize the cytoplasm and counteract molecular crowding. Using this model and independent parameter estimates we make predictions for the three energy scales that are in quantitative agreement with experimental values. The model also recapitulates the dependencies of cell growth with extracellular osmolarity and temperature. This theory brings together biophysics and cell biology in a tractable model that can be applied to understand key principles of cell metabolism.
维持细胞的维护，触发有氧发酵，并实现最大代谢率。有氧发酵和最大代谢率的转变目前基于酶成本的限制来理解。然而，我们缺乏一种解释维持能量需求的理论。在这里，我们报告了一个细胞代谢的物理模型，解释了这三个能量尺度的起源。我们的关键假设是，维持能量需求源于分子马达消耗的能量，以使细胞质流化并抵抗分子拥挤。使用这个模型和独立的参数估计，我们对三个能量尺度进行了预测，这些预测与实验值在数量上是一致的。该模型还概括了细胞生长与细胞外渗透压和温度的依赖性。这个理论将生物物理学和细胞生物学结合在一个可应用于理解细胞代谢关键原理的可处理模型中。
