Research Centre "E. Piaggio", University of Pisa, Pisa, Italy.
Department of Information Engineering, University of Pisa, Pisa, Italy.
Lab Chip. 2024 Aug 20;24(17):4128-4137. doi: 10.1039/d4lc00204k.
Accurate descriptions of the variability in single-cell oxygen consumption and its size-dependency are key to establishing more robust tissue models. By combining microfabricated devices with multiparameter identification algorithms, we demonstrate that single human hepatocytes exhibit an oxygen level-dependent consumption rate and that their maximal oxygen consumption rate is significantly lower than that of typical hepatic cell cultures. Moreover, we found that clusters of two or more cells competing for a limited oxygen supply reduced their maximal consumption rate, highlighting their ability to adapt to local resource availability and the presence of nearby cells. We used our approach to characterize the covariance of size and oxygen consumption rate within a cell population, showing that size matters, since oxygen metabolism covaries lognormally with cell size. Our study paves the way for linking the metabolic activity of single human hepatocytes to their tissue- or organ-level metabolism and describing its size-related variability through scaling laws.
准确描述单细胞耗氧量的可变性及其与细胞大小的相关性，对于建立更稳健的组织模型至关重要。通过结合微纳加工设备和多参数识别算法，我们证明了单个人类肝细胞表现出氧浓度依赖性的耗氧率，并且其最大耗氧率明显低于典型的肝细胞培养物。此外，我们发现两个或更多细胞簇争夺有限的氧供应会降低其最大耗氧量，这突出了它们适应局部资源可用性和邻近细胞存在的能力。我们使用我们的方法来描述细胞群体中大小和耗氧率的协方差，结果表明大小很重要，因为氧代谢与细胞大小呈对数正态相关。我们的研究为将单个人类肝细胞的代谢活性与其组织或器官水平的代谢联系起来，并通过尺度定律描述其与大小相关的可变性铺平了道路。
