Stiff substrates enhance monocytic cell capture through E-selectin but not P-selectin

Area of Science:

• Biomedical Engineering
• Immunology
• Cardiovascular Biology

Background:

• Vascular stiffening is linked to inflammatory diseases like atherosclerosis, diabetes, and obesity.
• Leukocyte recruitment into tissues drives these diseases, but the role of vascular stiffness is unclear.

Purpose of the Study:

• To investigate if leukocyte capture from blood flow is enhanced on stiffer substrates.
• To model in vitro blood flow and measure monocytic cell adhesion to E-selectin and P-selectin under varying stiffness conditions.

Main Methods:

• Perfusion of monocytic cells over hydrogels mimicking healthy and diseased artery stiffness.
• Hydrogels coated with endothelial adhesion proteins E-selectin or P-selectin.
• Quantification of cell attachment, duration, and rolling velocity.

Main Results:

• Cell attachment to P-selectin was independent of substrate stiffness.
• Attachment to E-selectin was enhanced on stiffer gels.
• Cells attached in greater numbers, for longer durations, and rolled slower on stiff E-selectin coated gels.

Conclusions:

• Vascular stiffening may promote leukocyte adhesion via E-selectin.
• The effect of vascular stiffening on leukocyte adhesion is dependent on the specific adhesion molecule involved.
• Arterial stiffness could contribute to leukocyte recruitment in inflammatory conditions where E-selectin is present.