title: Hydrogelation of the Short Self-Assembling Peptide I3QGK Regulated by Transglutaminase and Use for Rapid Hemostasis.
abstract: The self-assembly of short peptides is a promising route to the creation of smart biomaterials. To combine peptide self-assembly with enzymatic catalysis, we design an amphiphilic short peptide I3QGK that can self-assemble into long nanoribbons in aqueous solution. Upon addition of transglutaminase (TGase), the peptide solution undergoes a distinct sol-gel transition to form a rigid hydrogel, which shows strong shear-thinning and immediate recovery properties. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) measurements indicate the occurrence of considerable nanofibers in addition to the original nanoribbons. Liquid chromatography and mass spectrometry analyses reveal the enzymatic formation of peptide dimers from monomers through intermolecular ε-(γ-glutamyl)lysine isopeptide bonding. The dimers rapidly self-assemble into flexible and entangled nanofibers, and the coexistence of the original nanoribbons and the newly created nanofibers is responsible for hydrogelation. Factor XIII in blood is converted by thrombin to an active TGase (Factor XIIIa) during bleeding, so the peptide solution shows a more rapid and effective hemostasis via a combination of gelling blood and promoting platelet adhesion, relative to other hemostasis methods or materials. These features of I3QGK, together with its low cytotoxicity against normal mammalian cells and noninduction of nonspecific immunogenic responses, endow it with great potential for future clinical hemostasis applications.
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Centre for Bioengineering and Biotechnology, China University of Petroleum (East China) , 66 Changjiang West Road, Qingdao 266580, China.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Centre for Bioengineering and Biotechnology, China University of Petroleum (East China) , 66 Changjiang West Road, Qingdao 266580, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, College of Basic Medical Sciences, Jilin University , Changchun 130021, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Fei
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Centre for Bioengineering and Biotechnology, China University of Petroleum (East China) , 66 Changjiang West Road, Qingdao 266580, China.
authors.forename: Changhai
authors.initials: C
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Centre for Bioengineering and Biotechnology, China University of Petroleum (East China) , 66 Changjiang West Road, Qingdao 266580, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Centre for Bioengineering and Biotechnology, China University of Petroleum (East China) , 66 Changjiang West Road, Qingdao 266580, China.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Centre for Bioengineering and Biotechnology, China University of Petroleum (East China) , 66 Changjiang West Road, Qingdao 266580, China.
authors.forename: Jingkun
authors.initials: J
authors.lastname: Bai
authors.affiliation: Biological Physics Laboratory, School of Physics and Astronomy, The University of Manchester , Schuster Building, Manchester M13 9PL, United Kingdom.
authors.forename: Henry
authors.initials: H
authors.lastname: Cox
authors.affiliation: Biological Physics Laboratory, School of Physics and Astronomy, The University of Manchester , Schuster Building, Manchester M13 9PL, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Waigh
authors.affiliation: Biological Physics Laboratory, School of Physics and Astronomy, The University of Manchester , Schuster Building, Manchester M13 9PL, United Kingdom.
authors.forename: Jian R
authors.initials: JR
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Centre for Bioengineering and Biotechnology, China University of Petroleum (East China) , 66 Changjiang West Road, Qingdao 266580, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D005260:Female; D006490:Hemostatics / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D008099:Liver / Q000098:blood supply; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000633:toxicity; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011503:Transglutaminases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D006490:Hemostatics; D020100:Hydrogels; D037742:Nanotubes, Carbon; D009842:Oligopeptides; D011503:Transglutaminases
keywords: enzyme; hemostasis; hydrogel; self-assembly; short peptide