Substrate Stiffness Combined with Hepatocyte Growth Factor Modulates Endothelial Cell Behavior

Area of Science:

• Biomaterials Science
• Cell Biology
• Regenerative Medicine

Background:

• Endothelial cells (ECs) are vital for physiological and pathological processes.
• EC behavior is influenced by physical (stiffness) and biochemical cues (growth factors).
• The combined effects of these cues on ECs remain underexplored.

Purpose of the Study:

• To investigate the synergistic effects of substrate stiffness and hepatocyte growth factor (HGF) on endothelial cell behavior.
• To analyze how these combined cues influence endothelial function.
• To assess the potential for developing optimized biomaterials for regenerative medicine.

Main Methods:

• Fabrication of poly(l-lysine)/hyaluronan (PLL/HA) multilayer films with varying stiffness.
• Exposure of endothelial cells (ECs) to these substrates with and without HGF.
• Assessment of EC adhesion, migration, proliferation, monolayer integrity, nitric oxide production, and gene expression.

Main Results:

• EC adhesion, migration, and proliferation increased with substrate stiffness and were further enhanced by HGF.
• ECs on lower stiffness substrates showed a heightened response to HGF regarding migration and proliferation.
• Endothelial function, assessed via monolayer integrity and function markers, negatively correlated with substrate stiffness.
• HGF improved endothelial function but did not alter its stiffness-dependent nature.

Conclusions:

• Substrate stiffness and HGF synergistically modulate EC behavior, impacting both growth and function.
• Endothelial function is inversely related to substrate stiffness, a relationship not overcome by HGF.
• Findings offer insights for designing advanced biomaterials for endothelial cell-based regenerative medicine.