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Force-mediated kinetics of single P-selectin/ligand complexes observed by atomic force microscopy
J Fritz1, A G Katopodis, F Kolbinger
1Novartis Services AG, Scientific Services, Physics, WKL-127.620, CH-4002 Basel, Switzerland.
Summary
This study reveals how P-selectin glycoprotein ligand-1 interactions withstand high forces during leukocyte rolling. These molecular dynamics are crucial for immune cell adhesion and inflammation.
Area of Science:
- Biophysics
- Cellular and Molecular Biology
- Immunology
Background:
- Leukocyte rolling on endothelium is vital for inflammatory responses.
- This process relies on selectin-ligand interactions under blood flow forces.
- Understanding these molecular mechanics is key to controlling inflammation.
Purpose of the Study:
- To determine the intrinsic molecular properties of P-selectin/P-selectin glycoprotein ligand-1 interactions.
- To quantify the forces, elasticity, and kinetics governing leukocyte adhesion.
- To elucidate how these properties support physiological leukocyte rolling.
Main Methods:
- Utilized atomic force microscopy for force-spectroscopy experiments on single P-selectin/P-selectin glycoprotein ligand-1 complexes.
- Modeled intermolecular and intramolecular forces, and adhesion probability.
- Analyzed rupture forces, elasticity, and dissociation kinetics under varying forces.
Main Results:
- P-selectin/P-selectin glycoprotein ligand-1 complexes withstand forces up to 165 pN.
- Exhibited chain-like elasticity with a spring constant of 5.3 pN nm-1 and persistence length of 0.35 nm.
- Dissociation rates varied over three orders of magnitude, highly dependent on applied force and pulling velocity.
Conclusions:
- The P-selectin/P-selectin glycoprotein ligand-1 interaction possesses high binding strength and force-dependent kinetics.
- High molecular elasticity is a key feature supporting leukocyte rolling dynamics.
- These tailored molecular properties are essential for effective leukocyte adhesion in inflammation.