Nanoscale Mechanical Force Primes NOD1-LRR for Efficient Pathogen Recognition
Yang Ye1, Yong Zhang2,3, Jing Li4
1Kidney Disease Center of the First Affiliated Hospital and Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
The Journal of Physical Chemistry Letters
|October 20, 2025
Summary
NOD1 acts as a nanomechanical sensor, concentrating forces to detect bacterial ligands. This mechanochemical coupling enables rapid and precise innate immune activation against pathogens.
Area of Science:
- Innate Immunity
- Molecular Mechanobiology
- Nanobiology
Background:
- Cytosolic innate immune receptors, like NOD1, detect pathogens biochemically.
- The ability of these receptors to sense physical cues is largely unknown.
- Understanding mechanotransduction in innate immunity is crucial for pathogen detection.
Purpose of the Study:
- To investigate if NOD1 functions as a nanomechanical sensor.
- To elucidate the role of physical forces in NOD1-mediated pathogen recognition.
- To establish a new paradigm for cytosolic pathogen detection.
Main Methods:
- Piconewton-resolution single-molecule force spectroscopy.
- Molecular dynamics simulations.
- Structural modeling of the NOD1 receptor.
Main Results:
- NOD1's LRR domain acts as a mechanical force concentrator.
- Physiologically relevant forces prime NOD1 for conformational changes.
- Force-induced priming enhances binding affinity and sensitivity to bacterial ligand iE-DAP.
- Demonstrated mechanochemical coupling in NOD1 function.
Conclusions:
- NOD1 is an active nanomechanical sensor, not a passive detector.
- Mechanochemical coupling enables rapid and spatially restricted immune activation.
- Force-sensing LRR domains represent a generalizable design principle in nanobiology and innate immunity.
