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Immune cells use active tugging forces to distinguish affinity and accelerate evolution.

Hongda Jiang1, Shenshen Wang1

  • 1Department of Physics and Astronomy, University of California Los Angeles, Los Angeles, CA 90095.

Proceedings of the National Academy of Sciences of the United States of America
|March 10, 2023
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Cells use mechanical forces to drive their own evolution by extracting antigens, a process that can accelerate adaptation but also risks extinction. An optimal pulling strength balances these evolutionary outcomes.

Keywords:
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Area of Science:

  • Cell biology
  • Evolutionary biology
  • Biophysics

Background:

  • Cells sense physical surroundings for motion and fate decisions.
  • Immune B cells undergo rapid Darwinian evolution and extract antigens using cytoskeletal forces.

Purpose of the Study:

  • To investigate the evolutionary significance of cellular force usage.
  • To develop a theoretical framework for antigen extraction and its impact on clonal fitness.

Main Methods:

  • Developed a theory of tug-of-war antigen extraction.
  • Mapped receptor binding characteristics to clonal reproductive fitness.
  • Analyzed physical determinants of selection strength.

Main Results:

  • Cellular force usage can enhance adaptation but also increase extinction risk.
  • Optimal pulling strength balances extraction efficiency and discrimination stringency.
  • Active force usage is linked to molecular rupture forces.

Conclusions:

  • Nonequilibrium physical extraction of environmental signals can enhance evolvability.
  • Cellular mechanical work may drive evolution at a moderate energy cost.
  • Force-based antigen extraction unifies mechanosensing and affinity discrimination.