Cellular Thermometry Considerations for Probing Biochemical Pathways
Cellular Thermometry Considerations for Probing Biochemical Pathways
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DOI：
10.1007/s12013-021-00979-w
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发表时间：
2021-04-02
影响因子：
2.6
通讯作者：
Sinha，Sanjiv
中科院分区：
文献类型：
--
作者：
Rajagopal，Manjunath C.;Sinha，Sanjiv
温度是一种基本的热力学性质，可以作为生化反应的探针。细胞外测温术以前曾被用来探测癌症代谢和温度调节，测量到组织中的温度变化约为 1-2 K，与理论预测一致。相比之下，之前的细胞内测温研究仍然存在争议，因为有报道称细胞内温度在 5 分钟或更长时间内上升了 >1 K，这与理论不一致。因此，这种异常温度升高的根源仍不清楚。提高对细胞内测温的定量理解对于为未来的测量提供更清晰的视角是必要的。在这里，我们开发了一个通用框架，用于模拟一系列亚细胞到组织长度尺度上的细胞热扩散。我们的模型表明，只有在受到外源刺激时，局部细胞内温度变化才会达到可测量的极限（>0.1 K）。另一方面，即使通过内源生化途径，也可以在组织中测量细胞外温度（>0.1 K）。利用这些见解，我们通过分析从亚细胞到组织的长度尺度上不同热速率和时间常数的生热反应，提供了一种综合方法来选择合适的细胞测温技术。我们的工作阐明了细胞热扩散模型以及探测生热生化途径所需的测温方法。
Temperature is a fundamental thermodynamic property that can serve as a probe of biochemical reactions. Extracellular thermometry has previously been used to probe cancer metabolism and thermoregulation, with measured temperature changes of ~1–2 K in tissues, consistent with theoretical predictions. In contrast, previous intracellular thermometry studies remain disputed due to reports of >1 K intracellular temperature rises over 5 min or more that are inconsistent with theory. Thus, the origins of such anomalous temperature rises remain unclear. An improved quantitative understanding of intracellular thermometry is necessary to provide a clearer perspective for future measurements. Here, we develop a generalizable framework for modeling cellular heat diffusion over a range of subcellular-to-tissue length scales. Our model shows that local intracellular temperature changes reach measurable limits (>0.1 K) only when exogenously stimulated. On the other hand, extracellular temperatures can be measurable (>0.1 K) in tissues even from endogenous biochemical pathways. Using these insights, we provide a comprehensive approach to choosing an appropriate cellular thermometry technique by analyzing thermogenic reactions of different heat rates and time constants across length scales ranging from subcellular to tissues. Our work provides clarity on cellular heat diffusion modeling and on the required thermometry approach for probing thermogenic biochemical pathways.