Rolling adhesion of leukocytes on soft substrates: Does substrate stiffness matter?

Area of Science:

• Biophysics
• Cell Biology
• Biomaterials

Background:

• Cell rolling on vascular endothelium is crucial for physiological and pathological processes, including inflammatory responses and tumor metastasis.
• The mechanical properties of the endothelium, specifically its stiffness, are known to influence cell adhesion and motion, but the precise effects remain unclear.
• Understanding these interactions is vital for developing targeted therapies and diagnostic tools.

Purpose of the Study:

• To computationally model and investigate the effect of substrate stiffness on the adhesion and motion of rolling cells.
• To predict how variations in endothelial cell compliance impact cell rolling dynamics under hydrodynamic flow.
• To differentiate the influence of P-selectin and E-selectin mediated adhesion on cell rolling behavior in relation to substrate properties.

Main Methods:

• A computational model was developed to simulate the specific adhesion of a rolling cell onto a soft substrate under creeping shear flow.
• The substrate was modeled as an elastic half-space, functionalized with either P-selectin or E-selectin receptors.
• The model analyzed the kinematics and kinetics of cell motion, focusing on the impact of substrate compliance on adhesion and rolling velocity.

Main Results:

• The study found that substrate stiffness has a minimal effect on cell rolling when mediated by P-selectin.
• Conversely, the rolling trajectory and motion of cells on E-selectin coated substrates were significantly sensitive to substrate compliance.
• Increased substrate compliance led to moderated binding forces, resulting in a higher average translational velocity for rolling cells on E-selectin.

Conclusions:

• Endothelial cell stiffness plays a significant role in modulating cell rolling dynamics, particularly for E-selectin-mediated adhesion.
• The findings highlight the importance of considering the mechanical properties of the endothelium in understanding cell-substrate interactions.
• This research provides insights into the biomechanics of cell adhesion and motion, relevant for inflammatory and metastatic processes.