Self-assembling Beta-sheet Forming Peptide Biomaterials

This thesis deals with the development of novel strategies for self-assembling biomaterials based on short beta-sheet fibril-forming peptides. These materials are potentially useful for a variety of biomedical applications, including tissue engineering and controlled drug release, and several aspects of these materials have been explored in this thesis in an effort to improve their clinical utility. First, a strategy for rapidly and uniformly triggering peptide self-assembly was developed. Stimulus-sensitive liposomes were utilized to sequester salts and release them in response to stimuli such as warming to body temperature or exposure to near infra-red light. Triggered salt release in turn initiated rapid self-assembly of extravesicular peptide and the transformation of the peptide/liposome suspension from a solution to a hydrogel. We show that peptide self-assembly can be rapidly, uniformly, and specifically triggered, with the storage modulus increasing three orders of magnitude upon triggering. This rapid triggering strategy is potentially useful for injectable biomaterial applications. In the second research thrust, a self-assembling peptide was developed that also possessed enzymatic activity for the cross-linking enzyme tissue transglutaminase. We then utilized tissue transglutaminase to conjugate cell-interactive peptides to the self-assembled structure and investigated cell attachment to these functionalized scaffolds. Such a strategy is potentially useful for designing biospecific self-assembling scaffolds for tissue engineering or wound healing. In the final research focus, to modulate the nanostructure of the self-assembled fibrillar structures, we developed a series of self-assembling polyethylene glycol-conjugated peptides. We found that polyethylene glycol conjugation significantly altered fibril morphology, including width, length, and degree of lateral aggregation. As previous beta-sheet fibrillar self-assembled materials have shown particular intransigence to such modification of the fibrillar structure, this strategy may be a useful route for tailoring the physical properties of these materials. As a whole, the strategies developed in this thesis address previous shortcomings of beta-sheet peptide-based self-assembling materials in an effort to bring them closer to clinical application.

The self-organization of bionanostructures into well-defined functional machineries found in nature has been a priceless source of ideas for researchers. The molecules of life, proteins, DNA, RNA, etc., as well as the structures and forms that these molecules assume serve as rich sources of ideas for scientists or engineers who are interested in developing bio-inspired materials for innovations in biomedical fields. In nature, molecular self-assembly is a process by which complex three-dimensional structures with well-defined functions are constructed, starting from simple building blocks such as proteins and peptides. This book introduces readers to the theory and mechanisms of peptide self-assembly processes. The authors present the more common peptide self-assembled building blocks and discuss how researchers from different fields can apply self-assembling principles to bionanotechnology applications. The advantages and challenges are mentioned together with examples that reflect the state of the art of the use of self-assembled peptide building blocks in nanotechnology.

Self-assembling biomaterials: molecular design, characterization and application in biology and medicine provides a comprehensive coverage on an emerging area of biomaterials science, spanning from conceptual designs to advanced characterization tools and applications of self-assembling biomaterials, and compiling the recent developments in the field. Molecular self-assembly, the autonomous organization of molecules, is ubiquitous in living organisms and intrinsic to biological structures and function. Not surprisingly, the exciting field of engineering artificial self-assembling biomaterials often finds inspiration in Biology. More important, materials that self-assemble speak the language of life and can be designed to seamlessly integrate with the biological environment, offering unique engineering opportunities in bionanotechnology. The book is divided in five parts, comprising design of molecular building blocks for self-assembly; exclusive features of self-assembling biomaterials; specific methods and techniques to predict, investigate and characterize self-assembly and formed assemblies; different approaches for controlling self-assembly across multiple length scales and the nano/micro/macroscopic properties of biomaterials; diverse range of applications in biomedicine, including drug delivery, theranostics, cell culture and tissue regeneration. Written by researchers working in self-assembling biomaterials, it addresses a specific need within the Biomaterials scientific community. Explores both theoretical and practical aspects of self-assembly in biomaterials Includes a dedicated section on characterization techniques, specific for self-assembling biomaterials Examines the use of dynamic self-assembling biomaterials

Synthesis of Polypeptides by Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydrides, by Jianjun Cheng and Timothy J. Deming.- Peptide Synthesis and Self-Assembly, by S. Maude, L. R. Tai, R. P. W. Davies, B. Liu, S. A. Harris, P. J. Kocienski and A. Aggeli.- Elastomeric Polypeptides, by Mark B. van Eldijk, Christopher L. McGann, Kristi L. Kiick andJan C. M. van Hest.- Self-Assembled Polypeptide and Polypeptide Hybrid Vesicles: From Synthesis to Application, by Uh-Joo Choe, Victor Z. Sun, James-Kevin Y. Tan and Daniel T. Kamei.- Peptide-Based and Polypeptide-Based Hydrogels for Drug Delivery and Tissue Engineering, by Aysegul Altunbas and Darrin J. Pochan.-

Molecular self-assembly has been exploited by nature for developing the higher functional macromolecular structures of both the genome and proteome. Inspired by nature, there has been a surge of research, in the last two decades, for the molecular engineering of peptide-based self-assembling nanostructures, adopting the bottom-up design approach. This book gives the reader an overview on the design rules for de novo self-assembling peptide and reviews the diverse range of bioinspired peptide nanostructures such as β-sheet and β-hairpin, α-helical and coiled coil, self-assembling short peptides and peptidomimetics, collagen-based and elastin-like peptides, silk peptides, peptide amphiphiles, peptides co-polymers and others. The book also covers the wide variety of responsive and functional biomaterials that have been innovated based on those nanostructures for various applications ranging from tissue engineering, therapeutics and drug delivery to antimicrobial nanomaterials and biosensors. Finally, the book also discusses the peptide bionanomaterials global market and the future of the emerging industry. Chapter “Characterization of Peptide-Based Nanomaterials” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Solid-binding peptides have been used increasingly as molecular building blocks in nanobiotechnology as they can direct the assembly and functionalisation of a diverse range of materials and have the ability to regulate the synthesis of nanoparticles and complex nanostructures. Nanostructured materials such as β-sheet fibril-forming peptides and α-helical coiled coil systems have displayed many useful properties including stimulus-responsiveness, modularity and multi-functionality, providing potential technological applications in tissue engineering, antimicrobials, drug delivery and nanoscale electronics. The current situation with respect to self-assembling peptides and bioactive matrices for regenerative medicine are reviewed, as well as peptide-target modeling and an examination of future prospects for peptides in these areas.