In situ measurement of intracellular thermal conductivity using heater-thermometer hybrid diamond nanosensor

Abstract

Understanding heat dissipation processes at nanoscale during cellular thermogenesis is essential to clarify the relationships between the heat and biological processes in cells and organisms. A key parameter determining the heat flux inside a cell is the local thermal conductivity, a factor poorly investigated both experimentally and theoretically. Here, using a nanoheater/nanothermometer hybrid based on a polydopamine shell encapsulating a fluorescent diamond nanocrystal, we measured the intracellular thermal conductivity of HeLa cell with a spatial resolution of about 200 nm. Its mean value of 0.11 Wm -1 K -1 determined for the first time is significantly smaller than that of water. Bayesian analysis of the data strongly supports the existence of variation of the intracellular thermal conductivity of about 40%. These results present a major milestone towards understanding the intracellular heat transfer phenomena at nanoscale.

Cellular Thermometry Considerations for Probing Biochemical Pathways

“…If the local thermal resistances ( ′′ ) are in the order of 10 -4 K.m 2 W -1 at a lengthscale of 50 μm, the effective thermal conductivity is a strong function of the length scale varying from 0.05 Wm -1 K -1 to 0.25 Wm -1 K -1 , over 50 μm to 2 mm length-scale. Figure 3 shows that the effective thermal conductivity can be as low as ~0.05 Wm -1 K -1 at cellular length-scales (<50 μm), which is in close agreement with a recent report [55] of intracellular : 0.07-0.13 Wm -1 K -1 . We mark this experimentally reported thermal conductivity in red circle in Figure 3 at ~1.…”

“…) would be less than that of proteins (~0.1-0.2 Wm -1 K -1 ). This can happen at sub-cellular length-scales and has recently been observed in an intracellular effective thermal conductivity measurement [55], which reported a ~ 0.07-0.13 Wm -1 K -1 . To accurately capture the heat diffusion at sub-cellular length-scales, Equation (2) must be used as a boundary condition at the surfaces of biomolecular complexes while solving Equation (1).…”

“…We assumed a constant volumetric heat of dissipation per cell. The region in red corresponds to some of the previous experimental data points [28], [55], [63].…”

“…The − is representative of an average temperature measured using fluorescent dyes, or dispersed nanoparticles. If the heat input is known (say, endogenous heat source, or laser), the average temperature change can be used to estimate the local effective thermal conductivity, [55], [59]. Thus, in this study, we assume as the effective (or measured) thermal conductivity calculated using the volume averaged temperature ( − ) for a known volumetric heat source.…”

“…At sub-cellular length-scales, a recent report [55] measured the thermal conductivity to be 0.07-0.13 Wm -1 K -1 with a spatial resolution of 200 nm inside a cell. Since the measured is less than protein's thermal conductivity, (~0.1-0.2 Wm -1 K -1 ), the interfacial resistances ( ′′ ) possibly dominated at sub-cellular length-scales.…”