10.2 Nanoscale thermometry in living cells

Nanoscale thermometry in living cells is revolutionizing our understanding of cellular processes. By measuring temperature with incredible precision, we can now see how heat affects everything from protein folding to metabolic activity, giving us new insights into cell function and disease.

This cutting-edge technique uses quantum sensors like diamond nanoparticles to detect tiny temperature changes inside cells. It's opening up exciting possibilities for early disease detection, drug development, and unraveling the mysteries of how our cells work at the most fundamental level.

Nanoscale thermometry for living cells

Fundamentals and significance

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• Nanoscale thermometry measures temperature with 1-100 nanometer spatial resolution
• Provides insights into thermal gradients and fluctuations within living cells at the subcellular level
• Utilizes quantum sensors (nitrogen-vacancy (NV) centers in diamond) for high sensitivity and spatial resolution
• Reveals localized temperature changes associated with cellular processes and metabolic activities
• Detects subtle thermal signatures indicating disease states or cellular stress responses
• Enables potential early diagnosis of pathological conditions
• Enhances understanding of temperature variations in cellular functions
  • Mitochondrial activity
  • Protein folding
  • Enzymatic reactions

Applications in cellular biology

• Maps temperature gradients within cells and tissues with unprecedented spatial resolution
• Investigates role of localized temperature changes in cellular signaling and metabolic regulation
• Reveals previously unobservable thermal phenomena at the subcellular level
• Enhances understanding of heat generation and dissipation in biological systems at the nanoscale
• Facilitates study of thermogenesis in brown adipose tissue
  • Potential new approaches for treating obesity and metabolic disorders
• Enables detection of thermal signatures associated with cancer cells
  • Improves early diagnosis and treatment monitoring in oncology
• Provides insights into mechanisms of cellular stress responses and adaptation to environmental changes
  • Enhances understanding of cellular resilience and disease susceptibility

Quantum sensing techniques for nanoscale thermometry

Optical-based techniques

• Nitrogen-vacancy (NV) centers in diamond
  • Uses optically detected magnetic resonance (ODMR)
  • Measures temperature-dependent changes in NV center energy levels
  • Offers high sensitivity and spatial resolution
  • Requires optical access to the sample
• Fluorescent nanodiamonds
  • Employs temperature-dependent changes in fluorescence intensity or lifetime of NV centers
  • Provides good biocompatibility
  • Can be internalized by cells for intracellular measurements
• Lanthanide-doped nanoparticles
  • Exploits temperature-dependent changes in luminescence intensity ratio of different lanthanide ions
  • Offers ratiometric measurements
  • Reduces impact of variations in probe concentration or excitation intensity
• Quantum dots
  • Utilizes temperature-dependent shifts in fluorescence emission wavelength or intensity
  • Provides high brightness and photostability
  • May have limitations in cytotoxicity

Spin-based techniques

• Electron spin resonance (ESR)
  • Measures temperature-dependent changes in electron spin relaxation times
  • Offers non-invasive measurements
  • May have lower spatial resolution compared to optical techniques
• Nuclear magnetic resonance (NMR)
  • Utilizes temperature-dependent changes in nuclear spin relaxation times
  • Provides non-invasive measurements
  • Spatial resolution may be lower than optical methods

Challenges and opportunities of nanoscale thermometry

Technical challenges

• Maintaining viability and normal function of living cells while introducing nanoscale sensors
• Achieving sufficient signal-to-noise ratio in complex and dynamic cellular environments
• Minimizing phototoxicity and photobleaching associated with optical sensing techniques
• Ensuring accurate calibration and temperature referencing in heterogeneous cellular structures
• Developing biocompatible sensors that do not interfere with cellular processes or induce stress responses
• Improving spatial resolution of spin-based techniques to match optical methods
• Enhancing sensitivity to detect subtle temperature changes in cellular microenvironments
• Developing methods for long-term monitoring of temperature fluctuations in living systems

Opportunities and future directions

• Developing new diagnostic tools based on thermal signatures of diseased cells or tissues
• Combining nanoscale thermometry with other imaging modalities for multiparametric cellular analysis
• Investigating the role of temperature in regulating gene expression and epigenetic modifications
• Exploring the thermal properties of subcellular structures (membranes, cytoskeleton)
• Studying the impact of temperature on drug delivery and efficacy at the cellular level
• Developing temperature-responsive nanomaterials for targeted therapy and cellular manipulation
• Investigating the thermal aspects of cell-cell communication and tissue-level temperature regulation
• Applying nanoscale thermometry to study the thermodynamics of single-molecule reactions in living cells

Impact of nanoscale thermometry on cellular processes

Metabolic insights

• Detects subtle temperature changes associated with mitochondrial activity
• Provides insights into cellular energy metabolism and dysfunction
• Reveals localized heat generation during enzymatic reactions
  • Offers new perspectives on reaction kinetics and regulation in living cells
• Enables study of thermogenesis in brown adipose tissue
  • Potential applications in obesity and metabolic disorder treatments
• Investigates temperature-dependent changes in metabolic pathways
• Explores the relationship between local temperature and ATP production
• Examines the thermal signatures of different metabolic states (aerobic vs. anaerobic)

Protein dynamics and disease pathogenesis

• Investigates temperature-dependent protein folding and aggregation processes
  • Crucial for understanding neurodegenerative diseases (Alzheimer's, Parkinson's)
• Measures intracellular temperature gradients
  • Contributes to understanding of organelle-specific functions
  • Reveals role in cellular homeostasis
• Detects thermal signatures associated with cancer cells
  • Improves early diagnosis and treatment monitoring in oncology
• Examines the impact of temperature on protein-protein interactions and complex formation
• Investigates the role of temperature in regulating enzyme activity and substrate binding
• Studies the thermal aspects of protein degradation and quality control mechanisms