ArticleBiophysical journal2004
Molecular basis for the dynamic strength of the integrin alpha4beta1/VCAM-1 interaction.
Article in Biophysical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 116 citations in OpenAlex.
- Article
- The Endothelial Cell Perspective in Pulmonary Fibrosis: From Cell Fate Decisions, Intercellular Communication, and EndoMT to Emerging Therapies.Canadian respiratory journal · 2026Review
- VCAM-1 in Cognitive Impairment: Mechanisms, Biomarker Potential, and Therapeutic Targeting.Aging and disease · 2025Review
- FAIR data for optical tweezers experiments.Biophysical journal · 2025Review
- Biomechanics Model to Characterize Atomic Force Microscopy-Based Virus-Host Cell Adhesion Measurements.The journal of physical chemistry. B · 2024Article
- Characterization of the interaction between the Sec61 translocon complex and ppαF using optical tweezers.Protein science : a publication of the Protein Society · 2024Article
- Development of Biotinylated Liposomes Encapsulating Metformin for Therapeutic Targeting of Inflammation-Based Diseases.Pharmaceutics · 2024Article
- A novel anxiety-associated SNP identified inFrontiers in behavioral neuroscience · 2024Article
- The Force-Dependent Mechanism of an Integrin α4β7-MAdCAM-1 Interaction.International journal of molecular sciences · 2023Article
- Targeting endothelial vascular cell adhesion molecule-1 in atherosclerosis: drug discovery and development of vascular cell adhesion molecule-1-directed novel therapeutics.Cardiovascular research · 2023Review
- Macrophages and stem/progenitor cells interplay in adipose tissue and skeletal muscle: a review.Stem cell investigation · 2023Review
- Integrin Regulated Autoimmune Disorders: Understanding the Role of Mechanical Force in Autoimmunity.Frontiers in cell and developmental biology · 2022Review
- Biomechanical characterization of SARS-CoV-2 spike RBD and human ACE2 protein-protein interaction.Biophysical journal · 2021Article
- Length of mucin-like domains enhances cell-Ebola virus adhesion by increasing binding probability.Biophysical journal · 2021Article
- Multicellular contractility contributes to the emergence of mesothelioma nodules.Scientific reports · 2020Article
- Nintedanib Reduces Neutrophil Chemotaxis via Activating GRK2 in Bleomycin-Induced Pulmonary Fibrosis.International journal of molecular sciences · 2020Article
- The bioenergetics of integrin-based adhesion, from single molecule dynamics to stability of macromolecular complexes.Computational and structural biotechnology journal · 2020Review
- Dynamic bonds and their roles in mechanosensing.Current opinion in chemical biology · 2019Review
- Calcium-Mediated Biophysical Binding of Cryptosporidium parvum Oocysts to Surfaces Is Sensitive to Oocyst Age.Applied and environmental microbiology · 2019Article
- Distinct Binding Interactions of αBiophysical journal · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Intercellular adhesion mediated by integrin alpha4beta1 and vascular cell adhesion molecule-1 (VCAM-1) plays a crucial role in both the rolling and firm attachment of leukocytes onto the vascular endothelium. Essential to the alpha4beta1/VCAM-1 interaction is its mechanical strength that allows the complex to resist the large shear forces imposed by the bloodstream. Herein we employed single-molecule dynamic force spectroscopy to investigate the dynamic strength of the alpha4beta1/VCAM-1 complex. Our force measurements revealed that the dissociation of the alpha4beta1/VCAM-1 complex involves overcoming at least two activation potential barriers: a steep inner barrier and a more elevated outer barrier. The inner barrier grants the complex the tensile strength to withstand large pulling forces (>50 pN) and was attributed to the ionic interaction between the chelated Mg2+ ion at the N-terminal A-domain of the beta1 subunit of alpha4beta1 and the carboxyl group of Asp-40 of VCAM-1 through the use of site-directed mutations. In general, additional mutations within the C-D loop of domain 1 of VCAM-1 suppressed both inner and outer barriers of the alpha4beta1/VCAM-1 complex, while a mutation at Asp-143 of domain 2 of VCAM-1 resulted in the suppression of the outer barrier, but not the inner barrier. In contrast, the outer barrier of alpha4beta1/VCAM-1 complex was stabilized by integrin activation. Together, these findings provide a molecular explanation for the functionally relevant kinetic properties of the alpha4beta1/VCAM-1 interaction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.