Roles of cell and microvillus deformation and receptor-ligand binding kinetics in cell rolling

Area of Science:

• Biophysics
• Cellular Biology
• Immunology

Background:

• Polymorphonuclear leukocyte (PMN) recruitment is crucial for inflammatory responses.
• Selectin-mediated rolling of PMNs on endothelium is a key initial step.
• Previous models analyzed cell deformation, microvilli, and receptor-ligand bonds separately.

Purpose of the Study:

• To develop a computational model integrating multiple length scales (mesoscale, microscale, nanoscale) of cell rolling.
• To investigate the interplay between cell deformation, microvilli, and catch-slip bond dynamics in PMN rolling.
• To determine the relative contributions of these factors to the shear threshold phenomenon.

Main Methods:

• Developed a three-dimensional computational model.
• Integrated bulk cell deformation, microvillus deformability, and selectin-ligand bond kinetics.
• Simulated PMN rolling under various shear conditions and P-selectin site densities.

Main Results:

• Catch-slip bond behavior and bulk cell deformation significantly contribute to the shear threshold.
• Deformable microvilli lead to slower rolling only at high P-selectin densities and shear rates (>=400 s(-1)).
• More compliant cell membranes (1.2 dyn/cm) exhibit slower rolling than stiffer ones (3.0 dyn/cm) at shear rates >50 s(-1).

Conclusions:

• PMN rolling is a coordinated process influenced by forces across multiple length scales.
• The interplay between nanoscale bond dynamics, microscale features, and mesoscale deformation is critical for regulating PMN recruitment.
• This integrated model provides insights into the biophysical mechanisms governing inflammatory cell trafficking.