Engineering Heparan Sulfate-Guided Peptide Self-Assembly to Restore Endothelial Angiogenesis under Hyperglycemia

Area of Science:

• Biomaterials Science
• Vascular Biology
• Cellular Mechanics

Background:

• Hyperglycemia causes endothelial dysfunction, impairing cytoskeletal plasticity, cell migration, and angiogenesis, which drives diabetic vascular complications.
• This dysfunction involves impaired contractile homeostasis and increased cytoskeletal stiffness in endothelial cells.

Purpose of the Study:

• To engineer a heparan sulfate (HS)-targeting peptide for localized supramolecular nanostructure formation on the endothelial surface.
• To investigate the peptide's ability to restore endothelial mechanical function and vascular repair in vitro.

Main Methods:

• Development of a peptide combining a glycan-binding motif with a self-assembling domain.
• In vitro assessment of peptide-induced nanostructure formation and effects on endothelial cell mechanics (cytoskeletal stiffness, actomyosin contractility).
• Evaluation of endothelial cell migration, Matrigel tube formation assays, and cytotoxicity.

Main Results:

• The engineered peptide self-assembles into supramolecular nanostructures on the endothelial surface, guided by heparan sulfate.
• These nanostructures effectively reverse hyperglycemia-induced cytoskeletal stiffening and restore contractile homeostasis.
• The peptide enhances endothelial cell motility and promotes network formation in vitro without inducing cytotoxicity.

Conclusions:

• The HS-guided peptide platform offers a localized, biomimetic strategy to correct mechanical dysfunction in diabetic endothelium.
• This approach demonstrates translational potential for vascular repair in metabolic diseases by restoring endothelial function.