The local nano- and overall network structure, and resultant viscoelastic and cell-level biological properties, of hydrogels that are formed via beta-hairpin self-assembly will be presented.  Importantly, the hydrogels do not form until individual peptide molecules intramolecularly fold into a beta-hairpin conformation.  Subsequently, specific, intermolecular assembly occurs into a branched nanofibrillar network.  These peptide hydrogels are potentially excellent scaffolds for tissue regeneration and drug delivery due to inherent cytocompatibility, porous morphology, and shear-thinning but instant recovery viscoelastic properties. During assembly and gelation, desired components can be encapsulated within the hydrogel network such as drug compounds and/or living cells. The system can shear thin but immediately reheal to preshear stiffness on the cessation of the shear stress.  Recent adaptation of the materials to high throughput screening (HTS) will be described.  Automated cell-based high-throughput screening (HTS) is a powerful tool in drug discovery, and it is increasingly being recognized that three-dimensional (3D) cell culture models, which more closely mimic <i>in vivo</i>-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. Beta-hairpin peptide hydrogels can serve as a 3D cell culture platform that is compatible with HTS. MAX8 beta-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/>

Biomolecules for biomedical materials: Peptide design and solution assembly to construct nanostructures and hydrogel networks

2019 Fall National Meeting

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