Coassembly of amphiphilic peptide EAK16-II with histidinylated analogues and implications for functionalization of β-sheet fibrils in vivo

• Published in: Biomaterials Vol. 35; no. 19; pp. 5196 - 5205
• Main Authors: Wen, Yi, Roudebush, Shana L, Buckholtz, Gavin A, Goehring, Thomas R, Giannoukakis, Nick, Gawalt, Ellen S, Meng, Wilson S
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.06.2014
• Subjects: Advanced Basic Science; Amphiphilic peptides; Analogue; Animals; Biocompatibility; Biomedical materials; Cross-β fibrils; Dentistry; EAK16; Female; In vivo testing; In vivo tests; Mice; Mice, Inbred BALB C; Models, Molecular; Oligopeptides - chemistry; Oligopeptides - pharmacokinetics; Osmolar Concentration; Parents; Peptides; Peptides - chemistry; Peptides - pharmacokinetics; Protein formulation; Self-assembly; Surgical implants; Amphiphilic peptides; Self-assembly; Protein formulation; EAK16; Cross-β fibrils
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2014.03.009

Abstract EAK16-II (AEAEAKAKAEAEAKAK) is one of the first building blocks of environmentally responsive materials. This self-assembling peptide undergoes solution-to-gel transition when transferred from a low to high ionic strength environment. Previously we have demonstrated the histidinylated analogue EAKIIH6 (AEAEAKAKAEAEAKAKHHHHHH) coassembles with the parent peptide to render His-tags as a functionalization mechanism in vitro and in vivo . The present study aimed to understand the pathways by which the analogue coassembles with EAK16-II. The results presented herein suggested two competing but not mutually exclusive events in the coassembly. Atomic force microscopic and gel electrophoretic data showed that EAKIIH6 self-sorted to high molecular weight species without EAK16-II. Self-sorting of EAKIIH6 was inhibited by the parent peptide in a concentration dependent manner. Injecting mixtures containing EAKIIH6 subcutaneously rendered His-tags detectable in live mice for at least 312 h, despite diluting the histidinylated analogue by 10–50 folds compared to a previous formulation. The study provided a formulation by which in vivo display of His-tags was attained without excess amphiphilic peptides. By increasing coassembling efficiency, the likelihood of generating immunogenic aggregates outside the main fibrils could be minimized. These findings provide insights for rational functionalization of in situ self-gelling materials.