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Adv."],"published-print":{"date-parts":[[2026,7,31]]},"abstract":"<jats:p>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)\u2013mimetic amphiphile (SLan) with a mechanically robust \u03b2 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\u2013MEK (mitogen-activated protein kinase kinase)\u2013ERK (extracellular signal\u2013regulated 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.<\/jats:p>","DOI":"10.1126\/sciadv.aef5064","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:58:34Z","timestamp":1785520714000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Programming angiogenesis with tunable assemblies of multifunctional peptides"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2917-9896","authenticated-orcid":true,"given":"Joseph","family":"Dodd-o","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA."},{"name":"Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7132-2060","authenticated-orcid":true,"given":"Bobak","family":"Shadpoor","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9927-2544","authenticated-orcid":true,"given":"Abhishek","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0093-4085","authenticated-orcid":true,"given":"Roya","family":"Jafari","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarunya R.","family":"Sudarshan","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6719-8426","authenticated-orcid":true,"given":"Abigail","family":"Holberton","sequence":"additional","affiliation":[{"name":"George W. 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