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Beta-hairpin hydrogels as scaffolds for high-throughput drug discovery in three-dimensional cell culture.

Authors :
Worthington P
Drake KM
Li Z
Napper AD
Pochan DJ
Langhans SA
Source :
Analytical biochemistry [Anal Biochem] 2017 Oct 15; Vol. 535, pp. 25-34. Date of Electronic Publication: 2017 Jul 27.
Publication Year :
2017

Abstract

Automated cell-based high-throughput screening (HTS) is a powerful tool in drug discovery, and it is increasingly being recognized that three-dimensional (3D) models, which more closely mimic in vivo-like conditions, are desirable screening platforms. One limitation hampering the development of 3D HTS is the lack of suitable 3D culture scaffolds that can readily be incorporated into existing HTS infrastructure. We now show that β-hairpin peptide hydrogels can serve as a 3D cell culture platform that is compatible with HTS. MAX8 β-hairpin peptides can physically assemble into a hydrogel with defined porosity, permeability and mechanical stability with encapsulated cells. Most importantly, the hydrogels can then be injected under shear-flow and immediately reheal into a hydrogel with the same properties exhibited prior to injection. The post-injection hydrogels are cell culture compatible at physiological conditions. Using standard HTS equipment and medulloblastoma pediatric brain tumor cells as a model system, we show that automatic distribution of cell-peptide mixtures into 384-well assay plates results in evenly dispensed, viable MAX8-cell constructs suitable for commercially available cell viability assays. Since MAX8 peptides can be functionalized to mimic the microenvironment of cells from a variety of origins, MAX8 peptide gels should have broad applicability for 3D HTS drug discovery.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1096-0309
Volume :
535
Database :
MEDLINE
Journal :
Analytical biochemistry
Publication Type :
Academic Journal
Accession number :
28757092
Full Text :
https://doi.org/10.1016/j.ab.2017.07.024