"It's the questions we can't answer that teach us the most. They teach us how to think. If you give a man an answer, all he gains is a little fact. But give him a question and he'll look for his own answers. "
Patrick Rothfuss - The Wise Man's Fear
Multicomponent Polysaccharidebased synthetic ECMs
The challenge in development of surrogate extracellular matrices, ECMs is to design and prepare synthetic materials capable of influencing cell differentiation, proliferation, survival and migration through both biochemical interactions and mechanical cues. Current effort in the engineering of synthetic ECM has focused on installing molecular features (peptides, proteins and bio-interactive polymers) within insoluble scaffolds, either by self-assembly or through covalent modifications of polymer or biopolymer networks. Apart from their direct role in cell interaction, bioactive molecules or peptide sequences are found to affect the hierarchical structural organization and mechanical properties of the resulting material, thus affecting indirectly the cellular response. Specifically our researchdeals with studyingmulti-component polysaccharide hydrogels by characterizingthe self-assembled nanoscale morphology and local stiffness of their building blocks andevaluating the hydrogel resulting macroscale properties and
Peptide-Based Responsive and Bioactive Materials
Collaboration with the Matson group - VTech
Peptides exhibit rich, well-defined secondary structures, which in some cases change in response to a shift in temperature, pH, or other stimuli. Elastin-like peptides (ELPs) are thermoresponsive peptides inspired by the natural protein elastin. Comprised of a repeating pentameric sequence, linear ELPs have been widely studied as polymers that respond to temperature by changing their secondary structure and ultimately their solubility. Branched and dendritic ELPs, however, have received little attention. Our collaborators (The matson group,VT) has developed synthetic methods to make dendritic ELPs with high molecular weights, and we have discovered the branched structure of dendritic ELPs causes a shift in their transition temperature upon heating. We are now focused on incorporating branched ELPs into viscoelastic gels, with the goal of multiplying changes in peptide secondary structure across several orders of magnitude, from the molecular scale to the macroscale. Determining structure-property relationships in these peptide-based materials and measuring their effects on cell viability, proliferation, and differentiation are our major goals in this area of research.
Macroscopic sacs and membranes of hierarchically assembled biopolymers and peptides
One of the challenges in the field of biomaterials is the creation of complex scaffolds that can truly mimic the natural environment required for successful growth. Self-assembly of amphiphilic β-sheet and helical peptides were shown to be good candidates for the creation of complex synthetic ECMs. Combination of these peptide and biopolymers offer the potential to create a more sophisticated and better ECM mimetics.
The overall aim of the proposed research is to create macroscopic bio-functional, hierarchically self-assembled sacs and membranes by the amphiphilic and charged peptides and polysaccharides, to be utilized as multifunctional cell culture compartments.
