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Wylie Stroberg1, Santiago Schnell2

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Macromolecular crowding affects how accurately cells sense ligand concentrations. This study shows crowding can improve concentration accuracy for small ligands by enhancing association rates, but hinders it for large ligands.

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Area of Science:

  • Cellular Biology
  • Biophysics
  • Biochemistry

Background:

  • Signal transduction is vital for cell function and relies on accurate ligand concentration sensing by receptors.
  • The impact of macromolecular crowding on this sensing accuracy is not well understood.
  • Previous studies focused on dilute systems, leaving crowded cellular environments under-investigated.

Purpose of the Study:

  • To investigate how macromolecular crowding influences the accuracy of ligand concentration estimation by receptors.
  • To develop a computational method for simulating ligand-receptor interactions in crowded cellular environments.
  • To quantify the effects of crowding on reaction rates and correlation times.

Main Methods:

  • Developed a novel algorithm to simulate reversible reactions between Brownian particles.
  • Applied the algorithm to model ligand-receptor systems under conditions of macromolecular crowding.
  • Calculated reaction rates and correlation times to assess concentration inference accuracy.

Main Results:

  • Crowding can enhance the accuracy of ligand concentration estimation by increasing effective association rates for small ligands.
  • This enhancement in association rates can overcome increased rebinding due to molecular caging.
  • For larger ligands, crowding reduces sensing accuracy by decreasing microscopic association and dissociation rates.

Conclusions:

  • Macromolecular crowding has a significant, size-dependent impact on cellular ligand concentration sensing.
  • Crowding can be beneficial for sensing small molecules but detrimental for sensing larger ones.
  • Understanding these effects is crucial for comprehending cellular signaling in crowded physiological conditions.