MOLECULAR PACKING AND ORIENTATION OF SELF-ASSEMBLED PEPTIDE AMPHIPHILE SYSTEMS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Self-assembled nanostructures have been successfully exploited for a variety of purposes in medicine materials science and engineering. The proposed research centers on a particular kind of self-assembling molecule called peptide amphiphiles that form molecular hydrogels composed of nanofibers. These molecules have been utilized by our laboratory at Northwestern University to achieve a collection of bioengineering goals: as cell and tissue artificial scaffolds; as biomaterials that direct stem cell differentiation cell migration cellular response and tissue regeneration after injury; and as vehicles for cell peptide nucleic acid and protein delivery. Our experiments center on understanding supramolecular structures these molecules create by investigating molecular orientations and spatial distributions within the nanofiberous materials. The overall goal is to validate specific thermodynamic kinetic and molecular dynamic models of self-association and to uncover structure-function relationships of these engineered biomaterials. Future engineering of these specific molecules for biomedicine and therapeutics is contingent upon understanding all levels of the organizational behavior of these hydrogel systems. We believe that X-ray diffraction is an valuable addition to our present characterization methodologies by allowing molecular level resolution of this non-crystalline system. In particular the use of synchrotron X-ray sources will provide the highest level of resolution of molecular packing in contrast to other traditional polymer characterization methodologies. Collaboration with fiber diffractionists currently making great strides in understanding other peptide/protein-based self-assembling systems will lead to effective translation of techniques results and broader impact to society across both fields.