This award from the Biomaterials program in the Division of Materials Research to William Marsh Rice University is to study four peptide based, biomimetic self-assembling nanofibrous scaffolds, which provide mechanical strength and have controlled nanostructure. These nanofibrous scaffolds can be grouped based on the predominant peptide secondary structure found within each nanofiber. The first nanofiber is composed of Alpha-helical coiled-coils which self-assemble into a nanofibrous network under the proper conditions and with the appropriately designed amino acid sequence. These fibers have structural similarities to intermediate filaments such as the keratins. The second and third categories of nanofiber are composed of Beta-sheets and can be further subdivided into parallel and anti-parallel organization. These have structural similarities to the cross-beta spine organization of amyloid fibers. The fourth nanofiber has the same characteristic secondary structure and triple-helical organization as Collagen. These fibers allow the controlled placement of chemical functionality at the nanometer scale and are designed to have uniquely responsive and adaptive properties. This control over chemical functionality in a nanostructured environment makes them uniquely suited as biomimetic scaffolds for tissue regeneration. Fiber morphology is ubiquitous in nature. Some of the major biological nanofibers include actin filaments, intermediate filaments, microtubules and collagen. These fibers provide the structural organization and mechanical integrity of individual cells and, in the case of extracellular matrix proteins like collagen, of whole tissues. They also play critical roles in the transport of molecules, cell division and cell motility. Understanding these types of materials and specifically being able to create synthetic mimics of them is a highly desirable goal from both the perspective of enhancing our understanding of biological systems and from the perspective of nanotechnology.
The design, synthesis, characterization and biological application of these materials are part of an integrated research, teaching and outreach plan which will: 1) advance the cutting edge of our understanding of peptide folding and self-assembly; 2) help to elucidate the role of nanostructure in biological recognition and response; 3) push forward the boundaries of tissue engineering scaffold design; 4) be used to train post doctoral, graduate and undergraduate students in advanced interdisciplinary research which combines chemistry, biology and materials science; and 5) be used as a platform for outreach to under-represented secondary school students - and their teachers - in the greater Houston area demonstrating many of the current topics in science including nanotechnology, stem cell biology and bioengineering.
" funded research into the preparation of a variety of nanostructured materials. These materials were made through a process called self-assembly in which the building blocks organize themselves into fiberous materials. This process of self-assembly is commonly used in nature: for example to assemble the components that make up cells. Understanding this process and being able to mimic it in the laboratory has had two important outcomes: First, it allows us to understand biological processes in more detail which helps to lay the groundwork for further discoveries in biomedically related fields. Coming directly from the funding provided by this grant were substantial gains in our understanding of how collagen assembles into the triple helical and fiberous structure that binds the cells of our tissues together. Second, it has allowed us to prepare new, nanostructured materials which are now being used as a combined drug, protein and cell delivery vehicle critical for tissue regenerative strategies. The science funded by this grant has laid the groundwork for more in depth studies in collagen structure and assembly as well as advanced materials for tissue regeneration which are now being independently funded. While critical for the development of the science described above, this grant also provided, in part, for the funding of ten Ph.D. students, six of which are women. These students have all gone on to good jobs as in academia, government and industry. Two of these students are now tenure track faculty members.
