Intracellular Thermometry at the Micro‐/Nanoscale and its Potential Application to Study Protein Aggregation Related to Neurodegenerative Diseases

Abstract

Temperature is a fundamental physical parameter that influences biological processes in living cells. Hence, intracellular temperature mapping can be used to derive useful information reflective of thermodynamic properties and cellular behaviour. Herein, existing publications on different thermometry systems, focusing on those that employ fluorescence‐based techniques, are reviewed. From developments based on fluorescent proteins and inorganic molecules to metal nanoclusters and fluorescent polymers, the general findings of intracellular measurements from different research groups are discussed. Furthermore, the contradiction of mitochondrial thermogenesis and nuclear‐cytoplasmic temperature differences to current thermodynamic understanding are highlighted. Lastly, intracellular thermometry is proposed as a tool to quantify the energy flow and cost associated with amyloid‐β42 (Aβ42) aggregation, a hallmark of Alzheimer's disease.

Two-Photon Excitation of Silicon-Vacancy Centers in Nanodiamonds for All-Optical Thermometry with a Noise Floor of 6.6 mK·Hz–1/2

“…Temperature measurements with nanoscale resolution can provide unique information such as metabolic functions and life cycles within cells. , The development of nanothermometers is therefore critical for thermal biology. Diamond nanoparticles, also known as nanodiamonds (NDs), containing various fluorescent defects, have been proposed as promising nanothermometers due to their excellent thermal conductivity, remarkable photostability, attractive biocompatibility, and extreme chemical inertness. − In particular, nitrogen-vacancy (NV) centers have become a leading candidate over the past few years. ,− These centers enable precise temperature sensing based on their sensitive electron spin transitions. ,− Nevertheless, such a spin-based measurement requires microwave radiation, which might result in considerable temperature changes and interfere with biosystems .…”

“…Temperature measurements with nanoscale resolution can provide unique information such as metabolic functions and life cycles within cells. 1,2 The development of nanothermometers is therefore critical for thermal biology. Diamond nanoparticles, also known as nanodiamonds (NDs), containing various fluorescent defects, have been proposed as promising nanothermometers due to their excellent thermal conductivity, remarkable photostability, attractive biocompatibility, and extreme chemical inertness.…”

Intracellular thermometry uncovers spontaneous thermogenesis and associated thermal signaling

“…Around 2010, our group 27 and Yang et al 28 pioneered the detection of the temperature fluctuations inside of single living cells by combining fluorescent molecular thermometers introduced inside cells with optical microscopy. These achievements have accelerated the further establishment of intracellular temperature measurement methods using various fluorescent molecular thermometers or nonfluorescent metal materials represented by thermocouples; for more details about each method, their shortcoming, and uncertainties, as well as potential improvements, readers can refer to the invaluable review articles 29 – 35 . Thus, we here focus on the contribution of intracellular thermometry to thermal biology, avoiding repetitive descriptions of the comprehensive characteristics of the methods themselves.…”

Non-Interventional and High-Precision Temperature Measurement Biochips for Long-Term Monitoring the Temperature Fluctuations of Individual Cells

“…Semi-contact, temperature-sensitive fluorescence probes are widely designed to measure the cellular temperature distribution directly, in contradistinction to measurements of the fluorescence lifetime and intensity and the spectral-peak shift and anisotropy of fluorescent materials, including fluorescent polymers, lanthanide nanoparticles, quantum dots, nanodiamonds, and molecular beacons [8,9]. Fluorescent probes have the advantages of spatial resolution as high as hundreds of nanometers and thermal resolution of Biosensors 2021, 11, 454 2 of 12 0.01-1 K [10,11], but they are limited in accuracy and stability because the fluorescent materials are easily affected by the complex intracellular environment, which includes different ion concentrations, cytoplasmic viscosity, PH, and other factors [12,13].…”