Tunable Integrin–Ligand Coupling Strength Modulates Cellular Adaptive Mechanosensing
Cells sense and respond to the matrix by exerting traction force through binding of integrins to an integrin-specific ligand. Here, Arg-Gly-Asp (RGD) peptide is covalently conjugated to the double-stranded DNA (dsDNA) and stem-loop DNA (slDNA) tethers with a tension tolerance of 43pN and immobilized on a PEG substrate. Unlike dsDNA, which is ruptured under high tension, leading to the removal of RGD, slDNA remains bound even when ruptured. Our results suggest that cells adapt their adhesion state by modulating actin filament polymerization and cofilin phosphorylation, effectively balancing the talin conformation to prevent dsDNA rupture and maintain normal adhesion. This phenomenon, termed integrin-ligand coupling strength, mediated cellular adaptive mechanosensing. Furthermore, we demonstrate that positive durotaxis can shift to negative durotaxis, depending on the integrin-ligand coupling strength. This study highlights the significance of the coupling strength in cell-extracellular matrix (ECM) interactions and offers new insights into designing biomaterials with tunable adhesive properties for cell-based applications.
Authors
- Tian Jian Lu (ORCID: https://orcid.org/0000-0001-7795-7511)
- Feng Xu (ORCID: https://orcid.org/0000-0003-4351-0222)
- Guoqing Zhao (ORCID: https://orcid.org/0000-0002-0171-123X)
- Yu Zhang (ORCID: https://orcid.org/0000-0001-5510-1464)
- Ying Zhang (ORCID: https://orcid.org/0000-0003-4363-5666)
- Zheng Wang (ORCID: https://orcid.org/0000-0002-0490-466X)
- Xiaoxi Liu (ORCID: https://orcid.org/0000-0001-5917-5495)
- Zheng Zhang (ORCID: https://orcid.org/0000-0003-1961-7070)
- Min Lin
- Jinteng Feng (ORCID: https://orcid.org/0000-0002-1415-6423)
- Jin Yang (ORCID: https://orcid.org/0000-0001-8767-7214)
- Baoyong Sha
- Lingzhu Zhao
Institutions
- Ministry of Education of the People's Republic of China (CN)
- Wenzhou Medical University (CN)
- Xi'an Medical University (CN)
- First Affiliated Hospital of Xi'an Jiaotong University (CN)
- Zhejiang Lab (CN)
- Xijing Hospital (CN)
- Xi'an Jiaotong University (CN)
- Nanjing University of Aeronautics and Astronautics (CN)
- Air Force Medical University (CN)
Publication Details
- Journal
- Nano Letters
- Published
- 2025-03-07
- DOI
- https://doi.org/10.1021/acs.nanolett.4c05199
- Citations
- 2
- Primary Topic
- Cellular Mechanics and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 2.30
Funders
- National Natural Science Foundation of China
- Xi’an Jiaotong University
- Key Research and Development Projects of Shaanxi Province
- Natural Science Basic Research Program of Shaanxi Province
- National Institute of Biomedical Imaging and Bioengineering