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Published on: June 29, 2016
Effect of microvillus deformability on leukocyte adhesion explored using adhesive dynamics simulations
Kelly E Caputo1, Daniel A Hammer
1Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Biophysical Journal
|May 10, 2005
Summary
Leukocyte rolling, crucial for reaching infection sites, is better simulated using deformable microvilli. Microvillus mechanics, including viscosity and stiffness, optimize leukocyte adhesion and rolling dynamics.
Area of Science:
- Biophysics
- Cellular Mechanics
- Immunology
Background:
- Leukocyte rolling on endothelium is a key step in the immune response, enabling cells to reach infection sites.
- This process involves selectin molecules and is part of the broader cell adhesion cascade.
Purpose of the Study:
- To enhance Adhesive Dynamics simulations by incorporating deformable microvilli with clustered adhesion molecules.
- To investigate the impact of microvilli mechanics and receptor clustering on leukocyte rolling dynamics.
Main Methods:
- Modified Adhesive Dynamics simulations incorporating microvilli deformation (elastic spring at low force, yield/viscous dissipation at high force).
- Simulated effects of receptor clustering, adhesion molecule number, bond stiffness, and microvillus rheology.
- Compared simulation results with experimental data for in vitro cell rolling.
Main Results:
- Identified four adhesion states: firmly bound, landing, rolling, and no-adhesion.
- Found an optimal intermediate microvillus membrane viscosity for rolling velocity, close to physiological values.
- Demonstrated that increased membrane-cytoskeleton association slows rolling, while stiffer microvilli increase rolling speed.
Conclusions:
- Microvilli mechanics are finely tuned for leukocyte rolling and adhesion.
- Deformability of microvilli is essential for efficient leukocyte rolling.
- Simulations accurately predict experimental observations of cell rolling behavior, including pauses and stretches.
