Controlled sub-nanometer epitope spacing in a three-dimensional self-assembled peptide hydrogel
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Cells in the body use a variety of mechanisms to ensure the specificity and efficacy of signal transduction. One way that this is achieved is through tight spatial control over the position of different proteins, signaling sequences, and biomolecules within and around cells. For instance, the extracellular matrix protein fibronectin presents RGDS and PHSRN sequences that synergistically bind the α5β1 integrin when separated by 3.2 nm but are unable to bind when this distance is >5.5 nm.1 Building biomaterials to controllably space different epitopes with subnanometer accuracy in a three-dimensional (3D) hydrogel is challenging. Here, we synthesized peptides that self-assemble into nanofiber hydrogels utilizing the β-sheet motif, which has a known regular spacing along the peptide backbone. By modifying specific locations along the peptide, we are able to controllably space different epitopes with subnanometer accuracy at distances from 0.7 nm to over 6 nm, which is within the size range of many protein clusters. Endothelial cells encapsulated within hydrogels displaying RGDS and PHSRN in the native 3.2 nm spacing showed a significant upregulation in the expression of the alpha 5 integrin subunit compared to those in hydrogels with a 6.2 nm spacing, demonstrating the physiological relevance of the spacing. Furthermore, after 24 h the cells in hydrogels with the 3.2 nm spacing appeared to be more spread with increased staining for the α5β1 integrin. This self-assembling peptide system can controllably space multiple epitopes with subnanometer accuracy, demonstrating an exciting platform to study the effects of ligand density and location on cells within a synthetic 3D environment.
Date Issued
2016-11-27
Date Acceptance
2016-11-27
Citation
ACS Nano, 2016, 10 (12), pp.11096-11104
ISSN
1936-0851
Publisher
American Chemical Society
Start Page
11096
End Page
11104
Journal / Book Title
ACS Nano
Volume
10
Issue
12
Copyright Statement
© 2016 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano after peer review and technical editing by the publisher. To access the final edited and published work see https://dx.doi.org/10.1021/acsnano.6b05975
Sponsor
Commission of the European Communities
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000391079700053&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
PIEF_GA-2010-275433
Subjects
Science & Technology
Physical Sciences
Technology
Chemistry, Multidisciplinary
Chemistry, Physical
Nanoscience & Nanotechnology
Materials Science, Multidisciplinary
Chemistry
Science & Technology - Other Topics
Materials Science
self-assembly
peptides
cell-material interactions
hydrogels
integrins
fibronectin
synergy sequence
EXTRACELLULAR-MATRIX
SYNERGY SITE
INTEGRIN-BINDING
CELL-ADHESION
RGD
PHSRN
MORPHOGENESIS
FIBRONECTINS
SPECIFICITY
ENGAGEMENT
cell−material interactions
MD Multidisciplinary
Publication Status
Published