A Compressed Collagen Construct for Studying Endothelial-Smooth Muscle Cell Interaction Under High Shear Stress

Area of Science:

• Biomedical Engineering
• Vascular Biology
• Cellular Mechanics

Background:

• Investigating cellular interactions in blood vessel pathophysiology requires models that withstand wall shear stress (WSS).
• Previous collagen gel coculture models lacked the necessary stiffness for high WSS conditions.

Purpose of the Study:

• To develop a robust coculture model capable of withstanding higher WSS conditions.
• To investigate the effects of physiological and pathological WSS on vascular endothelial cells (ECs) and smooth muscle cells (SMCs) in a stiffer construct.

Main Methods:

• Constructed a centrifugally compressed cell-collagen combined construct (C6) with increased elastic modulus.
• Exposed the C6 model to WSS levels of 2 Pa (physiological) and 20 Pa (pathological).
• Analyzed the expression of α-smooth muscle actin, matrix metalloproteinases (MMPs), and MMP inhibitors.

Main Results:

• The C6 construct exhibited an elastic modulus approximately 6 times higher than uncompressed constructs.
• α-smooth muscle actin levels increased in C6, further elevated by 2 Pa WSS but not 20 Pa WSS.
• Differential expression ratios of MMPs and their inhibitors were observed in the C6 model under different WSS conditions, unlike in monocultures.

Conclusions:

• The C6 coculture model provides a mechanically stable platform for studying EC-SMC interactions under high WSS.
• This model is valuable for elucidating cellular responses to WSS relevant to blood vessel pathophysiology.
• The findings highlight differential cellular responses to physiological versus pathological WSS levels.