Self-Assembled Water-Soluble Nanofibers Displaying Collagen Hybridizing Peptides

Boi Hoa San, Jeongmin Hwang, Sujatha Sampath, Yang Li, Lucas L. Bennink, S. Michael Yu

Research output: Contribution to journalArticlepeer-review

Abstract

Collagen hybridizing peptides (CHP) have been demonstrated as a powerful vehicle for targeting denatured collagen (dColl) produced by disease or injury. Conjugation of β-sheet peptide motif to the CHP results in self-assembly of nonaggregating β-sheet nanofibers with precise structure. Due to the molecular architecture of the nanofibers which puts high density of hydrophilic CHPs on the nanofiber surface at fixed distance, the nanofibers exhibit high water solubility, without any signs of intramolecular triple helix formation or fiber-fiber aggregation. Other molecules that are flanked with the triple helical forming GlyProHyp repeats can readily bind to the nanofibers by triple helical folding, allowing facile display of bioactive molecules at high density. In addition, the multivalency of CHPs allows the nanofibers to bind to dColl in vitro and in vivo with extraordinary affinity, particularly without preactivation that unravels the CHP homotrimers. The length of the nanofibers can be tuned from micrometers down to 100 nm by simple heat treatment, and when injected intravenously into mice, the small nanofibers can specifically target dColl in the skeletal tissues with little target-associated signals in the skin and other organs. The CHP nanofibers can be a useful tool for detecting and capturing dColl, understanding how ECM remodelling impacts disease progression, and development of new delivery systems that target such diseases.

Original languageEnglish (US)
Pages (from-to)16640-16649
Number of pages10
JournalJournal of the American Chemical Society
Volume139
Issue number46
DOIs
StatePublished - Nov 22 2017
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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