Programming angiogenesis with tunable assemblies of multifunctional peptides.

Authors

Joseph Dodd-O, Bobak Shadpoor, Abhishek Roy, Roya Jafari, Tarunya R Sudarshan, Abigail Holberton, Dongjing He, Francesco Coppola, Daniel M Dinakarapandian, Deep Malu, Gelavizh Gharati, Alexandra Griffith, Harrison Rohe-Weiner, Siya Patel, Edward Bonder, Yuhang Hu, Levi Wood, Anant K Paravastu, Petr Kral, Vivek A Kumar

Published in

Science advances. Volume 12. Issue 31. Pages eaef5064. Jul 31, 2026. Epub Jul 31, 2026.

Abstract

Therapeutic angiogenesis is constrained by the inability to localize, sustain, and finely tune vascular signaling. Here, we detail a supramolecular peptide system that enables angiogenic programming by decoupling mechanical integrity from receptor-level bioactivity. We integrate a vascular endothelial growth factor (VEGF)-mimetic amphiphile (SLan) with a mechanically robust β sheet peptide (K1) to yield injectable nanofiber hydrogels with tunable stiffness (100 to 1000 pascals) and preserved vascular endothelial growth factor receptor 2 (VEGFR2) affinity. Molecular dynamics simulations and solid-state nuclear magnetic resonance revealed that the coassembly mitigates steric interference between domains, enabling dense supramolecular packing while maintaining optimal receptor accessibility. The resulting SLan-K1 formulation preserves the secondary structure, activating canonical VEGFR2-MEK (mitogen-activated protein kinase kinase)-ERK (extracellular signal-regulated kinase). In vitro, these hydrogels induce endothelial proliferation; in vivo, they drive rapid neovascular infiltration and stable vascular integration in murine and rodent implants. This design unites peptide self-assembly, receptor binding kinetics, and immunophenotypic outcomes in defining a molecular framework for tunable angiogenic materials. This strategy establishes a modular platform for engineering instructive microenvironments that bridge molecular design and tissue-scale functionality.

PMID:
42536725
Bibliographic data and abstract were imported from PubMed on 01 Aug 2026.

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