Peptide self assembly: peptide chemistry effects on nanofiber formation mechanisms and in-gel enzymatic activity

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Self-assembling peptide hydrogels, composed of nanofibers with nanoscale dimensions, are becoming recognized as a robust platform for a variety of applications: delivering active proteins and small molecules. Preliminary studies indicate a lack of immune response or initiation of the coagulation cascade to these materials: the mechanisms of which remain unknown. These properties, plus the ability to precisely control the peptide sequence, and thereby incorporate enzymatic cleavage domains, peptide therapeutics, etc., makes self-assembled peptide hydrogels very attractive. However, it remains apparent that several aspects involved in the design of these materials is ill-defined: effect of peptide chemistry on nanofiber formation, effect of peptide chemistry on vicinal water structure within the hydrogel, subsequent effects on molecular mobility within the hydrogel, in-gel regional viscosities, fundamental mechanisms involved in peptide self assembly, and finally the effect of these factors upon the interaction with a complex biological milieu. Although work has progressed in this area, this grant will build upon what has already been learned over the past 4 years of work supported by the NSERC-Discovery Grant; which has been achieved through the training of two graduate students and several undergraduate researchers. Through understanding the effects of the peptide composition on gel properties as well as protein interactions, it may be possible to develop these materials for multiple technologies: enzymatically controlled drug delivery, tissue engineering scaffolds to enhance wound healing, high surface area biosensors, cardiovascular grafts, etc.