The extracellular matrix (ECM) plays a crucial role in providing both physical and chemical cues which guide essential processes such as cell migration, proliferation and differentiation. A number of materials have attempted to mimic the physical and chemical structure of this fibrillary extracellular matrix. One class of materials that has recently received attention is self-assembling peptide hydrogels, which self-assemble into one dimensional fibres through non-covalent interactions, before cross-linking to form hydrogels. They represent attractive candidates for mimicking the native ECM as their self-assembly is reversible (resulting in dynamic behaviour) and both physical and chemical properties can be tuned.

However, although there is much promise surrounding the use of peptide hydrogel scaffolds for tissue engineering, drug delivery and high throughput screening applications, little is understood about how to tune their physical and chemical properties in a controllable manner with a view towards scaffolding specific cell populations.

Here, I will present our latest work on rationally designing and controlling the self-assembly of a novel class of water-soluble tetrapeptides which self-assemble into biocompatible hydrogels. We use these hydrogels to support sensitive primary neurons, the current gold standard in neuronal cell culture, for up to 40 days in vitro, with key milestones including synaptogenesis and electrical signaling observed. We show that the order of peptide sequences influences cell fate, and that the method of gelation plays an important role in this process. We envision these materials having potential applications in providing insights into the behavior of healthy and abnormal neurons in a controllable in vitro setting.