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Theoretical limits for sensing through phase separation.

Henry Alston1, Mason Rouches2, Arvind Murugan2

  • 1Laboratoire de physique de l'École normale supérieure, CNRS, Paris Sciences et Lettres University, Sorbonne Université, and Université Paris-Cité, Paris 75005, France.

Proceedings of the National Academy of Sciences of the United States of America
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PubMed
Summary
This summary is machine-generated.

Cells use phase separation to rapidly sense small molecule concentration changes. This biomolecular condensate formation mechanism allows for quick cellular responses to environmental shifts within minutes.

Keywords:
biological concentration sensingcellular decision-makingdropletliquid–liquid phase transition

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Area of Science:

  • Cell biology
  • Biophysics
  • Biochemistry

Background:

  • Biomolecular condensates form rapidly in response to cellular changes.
  • Condensate formation is proposed as a mechanism for sensing environmental shifts and initiating cellular processes.
  • Examples include stress granule formation and amplification of cyclic GMP-AMP synthase activity.

Purpose of the Study:

  • To investigate how phase separation enables cells to detect small concentration differences.
  • To analyze the dynamics of droplet nucleation and growth in condensate formation.
  • To propose optimal sensing protocols leveraging the phase separation phenomenon.

Main Methods:

  • Development of a dynamical model for droplet nucleation and growth.
  • Analysis of phase separation dynamics.
  • Incorporation of experimentally measured rates into the model.

Main Results:

  • Phase separation allows discrimination of small concentration differences on biologically relevant timescales.
  • Optimal sensing protocols utilizing the sharp onset of phase separation were proposed.
  • Cells can achieve rapid and robust sensing of concentration differences within minutes.

Conclusions:

  • Phase separation provides a mechanism for rapid and sensitive cellular detection of concentration changes.
  • This process offers an alternative to classical biochemical sensing mechanisms.
  • Biomolecular condensates play a crucial role in cellular environmental sensing and response.