ArticleProceedings of the National Academy of Sciences of the United States of America2023
Immune cells use active tugging forces to distinguish affinity and accelerate evolution.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Dynamics of local B cell migration during affinity maturation in the human tonsil.bioRxiv : the preprint server for biology · 2025Article
- Review
- Mechanical interactions impact the functions of immune cells and their application in immunoengineering.Advanced therapeutics · 2025Article
- Antigen mobility regulates the dynamics and precision of antigen capture in the B cell immune synapse.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Compressive stresses in cancer: characterization and implications for tumour progression and treatment.Nature reviews. Cancer · 2024Review
- Physical extraction of antigen and information.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mechanical control of antigen detection and discrimination by T and B cell receptors.Biophysical journal · 2024Review
- Extracellular matrix rigidity modulates physical properties of subcapsular sinus macrophage-B cell immune synapses.Biophysical journal · 2024Article
- The effects of matrix stiffness on immune cells in bone biology.Mechanobiology in medicine · 2024Review
- Theory and Examples of Catch Bonds.The journal of physical chemistry. B · 2024Article
- Evidence and therapeutic implications of biomechanically regulated immunosurveillance in cancer and other diseases.Nature nanotechnology · 2024Review
- Mechanical forces amplify TCR mechanotransduction in T cell activation and function.Applied physics reviews · 2024Review
- A physical tug-of-war and the evolution of immune cells.Journal of biosciences · 2023Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Cells are known to exert forces to sense their physical surroundings for guidance of motion and fate decisions. Here, we propose that cells might do mechanical work to drive their own evolution, taking inspiration from the adaptive immune system. Growing evidence indicates that immune B cells-capable of rapid Darwinian evolution-use cytoskeletal forces to actively extract antigens from other cells' surfaces. To elucidate the evolutionary significance of force usage, we develop a theory of tug-of-war antigen extraction that maps receptor binding characteristics to clonal reproductive fitness, revealing physical determinants of selection strength. This framework unifies mechanosensing and affinity-discrimination capabilities of evolving cells: Pulling against stiff antigen tethers enhances discrimination stringency at the expense of absolute extraction. As a consequence, active force usage can accelerate adaptation but may also cause extinction of cell populations, resulting in an optimal range of pulling strength that matches molecular rupture forces observed in cells. Our work suggests that nonequilibrium, physical extraction of environmental signals can make biological systems more evolvable at a moderate energy cost.
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