This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project II: Schneider and Pochan Hydrogels, a class of materials integral to biotechnologies such as tissue engineering and microfluidics are classically made from high molecular weight polymers. Ideal hydrogel scaffolds for use in tissue engineering are easily synthesized using non-toxic chemistries, biocompatible, promote cell adhesion/proliferation and are biodegradable. In terms of material properties, their morphology should be porous for cell motility and nutrient/waste diffusion. However, despite their porous nature, these materials must be mechanically rigid. We developed an alternate strategy that employs self-assembling peptides to prepare responsive hydrogels. Preparing materials from peptides is advantageous since peptides are quickly synthesized and novel amino acid residues readily incorporated for tailored functions. Also, since our hydrogels are prepared from a pure self-assembly mechanism, there is no need for exogenous toxic cross linking agents. The strategy employs designed peptides that intramolecularly fold on cue into a b-hairpin conformation that is amenable to self-assembly. Key to this system is that the peptide must be intramolecularly folded before self-assembly leading to hydrogelation can occur. By designing peptides that only fold when desired environmental cues are present, responsive materials may be constructed. Hairpins have been designed to fold in response to pH and ionic strength changes, light, and temperature changes. Hydrogels are porous and well hydrated on the micro- and nano-scale, but are rigid (G'=1600Pa), shear thin and self heals after cessation of shear. Importantly, these hydrogels support the attachment and proliferation of NIH 3T3 fibroblasts (mouse), indicating their possible use as tissue engineering scaffolds.