Matrix stiffness regulates the interactions between endothelial cells and monocytes

Area of Science:

• Biomaterials Science
• Vascular Biology
• Cellular Mechanics

Background:

• Endothelial cells (ECs) form a critical barrier, and monocyte recruitment to ECs initiates vascular diseases like atherosclerosis.
• Vascular EC functions are influenced by biochemical factors, hemodynamic forces, and matrix stiffness, which changes with aging and disease.
• The precise role of matrix stiffness in EC-monocyte interactions remains unclear.

Purpose of the Study:

• To investigate the impact of matrix stiffness on monocyte chemotaxis and adhesion to ECs.
• To elucidate the molecular mechanisms, including microRNA (miRNA) involvement, mediating these stiffness-dependent interactions.

Main Methods:

• ECs were cultured on matrices of varying stiffness (8, 20, and 40 kPa).
• Monocyte chemotaxis and adhesion assays were performed.
• Expression levels of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), miR-126, and miR-222 were analyzed.
• Inhibition of miR-126 and miR-222 was used to assess their role in mediating stiffness effects.

Main Results:

• ECs on soft (8 kPa) and stiff (40 kPa) matrices exhibited enhanced chemotactic effects on monocytes compared to 20 kPa matrices.
• Monocyte adhesion followed a similar pattern, correlating with increased VCAM-1 and ICAM-1 expression on softer and stiffer matrices.
• miR-126 and miR-222 expression showed an inverse correlation with VCAM-1 and ICAM-1, respectively.
• Inhibiting miR-126 and miR-222 abolished the matrix stiffness-dependent effects on monocyte adhesion, indicating their mediating role.

Conclusions:

• Matrix stiffness significantly regulates EC-monocyte interactions, influencing monocyte recruitment and adhesion.
• miR-126 and miR-222 mediate the effects of matrix stiffness on VCAM-1 and ICAM-1 expression, thereby controlling monocyte adhesion.
• These findings offer insights into vascular disease pathogenesis, aging, and provide a basis for vascular tissue engineering and therapeutic strategies.