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Determination of Protein-ligand Interactions Using Differential Scanning Fluorimetry
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Precision of Protein Thermometry.
Michael Vennettilli1,2, Soutick Saha2, Ushasi Roy2,3
1Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Physical Review Letters
|September 10, 2021
Summary
Cells precisely sense temperature using internal protein factors, not external fluctuations. This protein-based mechanism allows accurate temperature estimation within 2%, revealing fundamental limits in cellular thermoreception.
Area of Science:
- Cellular biology
- Biophysics
- Microbiology
Background:
- Temperature sensing is vital for cell survival and function.
- The precision limits of cellular temperature sensing are not well understood.
- Unlike chemical sensing, temperature sensing precision is not limited by external temperature variations.
Purpose of the Study:
- To investigate the fundamental limits of temperature sensing precision in cells.
- To identify the key molecular factors governing cellular thermoreception accuracy.
- To develop a biophysical model for predicting temperature sensing precision.
Main Methods:
- Developed a biophysical model based on the TlpA thermosensor protein.
- Analyzed the roles of protein copy number, turnover rate, and binding kinetics.
- Compared model predictions with in vivo experimental data from bacterial temperature sensing.
Main Results:
- Cellular temperature sensing precision is limited by intrinsic molecular properties, not external temperature fluctuations.
- Key factors include the copy number, turnover, and binding kinetics of temperature-sensitive proteins.
- A model based on TlpA predicts temperature estimation accuracy within 2%.
Conclusions:
- Intrinsic molecular properties, not environmental noise, dictate the precision of cellular temperature sensing.
- The TlpA model provides a quantitative framework for understanding thermoreception limits.
- This work advances our understanding of fundamental biophysical constraints in cellular sensing mechanisms.

