TY - JOUR
T1 - Self-Assembled Water-Soluble Nanofibers Displaying Collagen Hybridizing Peptides
AU - San, Boi Hoa
AU - Hwang, Jeongmin
AU - Sampath, Sujatha
AU - Li, Yang
AU - Bennink, Lucas L.
AU - Yu, S. Michael
PY - 2017/11/22
Y1 - 2017/11/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85034825264&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85034825264&partnerID=8YFLogxK
U2 - 10.1021/jacs.7b07900
DO - 10.1021/jacs.7b07900
M3 - Article
C2 - 29091434
AN - SCOPUS:85034825264
VL - 139
SP - 16640
EP - 16649
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 46
ER -