Extracellular matrix composition alters endothelial force transmission.

Area of Science:

• Biomedical Engineering
• Cellular Biomechanics
• Vascular Biology

Background:

• Extracellular matrix (ECM) composition changes are observed in pathophysiological processes like atherosclerosis and diabetes.
• The mechanical response of endothelium to varying ECM compositions is not well understood.
• Vascular diseases may involve a shift in ECM from collagen-rich to fibronectin-rich.

Purpose of the Study:

• To investigate the impact of different collagen I (Col-I) and fibronectin (FN) ratios on endothelial cell biomechanics and morphology.
• To quantify endothelial cell tractions, intercellular stresses, strain energy, and cell shape under defined ECM conditions.

Main Methods:

• Human umbilical vein endothelial cells (HUVECs) were cultured on soft hydrogels coated with varying Col-I:FN ratios (100:0, 75:25, 50:50, 25:75, 0:100) at 0.1 mg/mL.
• Measurements included cell tractions, intercellular stresses, strain energy, cell morphology (area, circularity), and cell velocity.

Main Results:

• Peak tractions and strain energy were observed at the 50% Col-I-50% FN ratio, with minimal values at 100% Col-I and 100% FN.
• Intercellular stress response was highest at 50% Col-I-50% FN and lowest at 25% Col-I-75% FN.
• Cell area and circularity showed distinct responses to different Col-I and FN ratios.

Conclusions:

• Endothelial cell biomechanical and morphological responses are significantly influenced by the ratio of collagen I to fibronectin in the extracellular matrix.
• The 50% Col-I-50% FN composition appears optimal for endothelial cell mechanical activity.
• These findings have implications for understanding vascular physiology and pathology, particularly in diseases involving ECM remodeling.