TY - JOUR
T1 - Cellular Thermometry Considerations for Probing Biochemical Pathways
AU - Rajagopal, Manjunath C.
AU - Sinha, Sanjiv
N1 - Funding Information:
We thank Dr. Jeffrey Brown, Prof. Daniel Llano, and Prof. Rhanor Gillette for their useful inputs throughout this work. Figure was made in part using biorender.com . This work was supported in part by funding from the National Science Foundation through Grant No. NSF-CBET-17-06854.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - Cellular metabolism
KW - Design of experiments
KW - Heat diffusion
KW - Interfacial resistance
KW - Intracellular thermometry
KW - Thermal conductivity
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U2 - 10.1007/s12013-021-00979-w
DO - 10.1007/s12013-021-00979-w
M3 - Article
C2 - 33797706
AN - SCOPUS:85103676383
VL - 79
SP - 359
EP - 373
JO - Cell Biochemistry and Biophysics
JF - Cell Biochemistry and Biophysics
SN - 1085-9195
IS - 2
ER -