DataVXThe Journal of Physical Chemistry LettersPaper
journal article·2025-10-30

Nanoscale Mechanical Force Primes NOD1-LRR for Efficient Pathogen Recognition

Yang Ye, Yong Zhang, Jing Li, Peng Wu, Tongtong Zhang, Tailin Liao, Dante Neculai, Jizhong Lou, Zhenhai Li, Wei Chen, Wei Hu

The Journal of Physical Chemistry Letters· Volume 16· Issue 43
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Source abstract

Abstract

Detecting pathogens requires molecular sensors that can rapidly and precisely respond to local threats. While cytosolic innate immune receptors such as NOD1 are known as biochemical detectors, their ability to interpret physical cues remains a critical unknown. Here, we combine piconewton-resolution single-molecule manipulation, molecular dynamics simulations, and structural modeling to demonstrate that NOD1 is not a passive detector but an active nanomechanical sensor. We show that the receptor's LRR domain, with its curved, horseshoe-like nanoarchitecture, functions as a mechanical force concentrator. Physiologically relevant piconewton-scale forces, such as those at the membrane-cytosol interface, are concentrated into a high-stress hotspot that primes the domain for a conformational transition. This force-induced priming acts as an allosteric nanoswitch, transducing mechanical energy into a biochemical output: a dramatic increase in binding strength and sensitivity for its bacterial ligand iE-DAP. This mechanochemical coupling positions NOD1 as a force-responsive sensor, enabling rapid and spatially restricted immune activation. Our work establishes a new paradigm for cytosolic pathogen recognition and suggests that force-sensing LRR domains represent a generalizable design principle in nanobiology, bridging a conceptual gap between mechanobiology and innate immunity.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Force Microscopy Techniques and Applications · Cellular Mechanics and Interactions · Lipid Membrane Structure and Behavior

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Kidney Disease Center of the First Affiliated Hospital and Department of Cell Biology

Zhejiang University

State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics

Chinese Academy of Sciences

University of Chinese Academy of Sciences

Shanghai Key Laboratory of Mechanics in Energy Engineering, Shanghai Institute of Applied Mathematics and Mechanics, School of Mechanics and Engineering Science

Shanghai University

State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences

Zhengzhou University

Department of Obstetrics and Gynecology, Affiliated Hangzhou First People’s Hospital, School of Medicine

Westlake University

Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Liangzhu Laboratory

Department of Respiratory and Critical Care Medicine, Center for Metabolism Research

The Fourth Affiliated Hospital of Zhejiang University School of Medicine, International School of Medicine, International Institutes of Medicine, Zhejiang University

Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Education Frontier Science Center for Brain Science & Brain-machine Integration, State Key Laboratory for Modern Optical Instrumentation Key Laboratory for Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering and Instrument Science

Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Institute of Nephrology

Funding

National Natural Science Foundation of China · Natural Science Foundation of Zhejiang Province

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