| dc.description.abstract | In Nature, molecular self-assembly plays a critical role in the formation of complex biological structures and functions and is omnipresent in biological materials and systems. The dynamic interactions driven by the molecular self-assembly have been at the core of highly organized structures spanning the nano-, micro-, and macroscopic scales. Mimicking the self-assembly process in biological systems at the molecular scale led to the emerging field of molecular biomimetics, building upon the significant advances in biology, chemistry, material sciences, engineering, and medicine over the past three decades. The premise of molecular biomimetics is the development of hybrid engineering principles, where biomolecular tools can be incorporated in the design of advanced materials, processes, and systems. Recognized as the fundamental building blocks in biological systems, peptides and proteins play a key role in molecular recognition and self-assembly. Over the past few decades, solid-binding peptides have been identified and designed as molecular assemblers with material-selective affinities. These peptides demonstrate the ability to self-assemble at the surfaces and interfaces of solid materials and guide additional moieties to be anchored at site-specific positions. Building upon their bio-enabled surface and interfacial properties, several of these solid-binding peptides have been shown to develop novel hybrid materials. With inherent advantages over conventional chemical methods including ease of design and synthesis and modular design potential to offer multi-functional properties, these solid binding peptides have attracted increasing attention as a promising bio-enabled approach to design self-assembled, bioactive materials and systems for various applications across biotechnology, nanotechnology, and biomedical sciences. Vast libraries of solid-binding peptides, known also as genetically engineered peptides for inorganics (GEPIs), have been identified in the past decades using principles of combinatorial biology and protocols such as phage- and cell-surface display technologies. Identified peptides are subject to extensive qualitative and quantitative characterization to investigate their material-binding properties under different conditions. Peptide binding and assembly properties are merged with the computational approaches to investigate their sequence-structure-function properties. The iterative design of the peptides builds upon detailed experimental and computational approaches to enhance their properties specific to materials and desired applications. Using high-affinity peptides and building upon their modular design potential at complex biomaterial interfaces, multifunctional biohybrid platforms can be designed where additional biological activities can be incorporated. Each application introduces new challenges with respect to their unique surface or interface in addition to the function in a desired environment. The peptide self-assembly depends on several factors ranging from physicochemical to environmental factors, and biological environments introduce another level of complexity due to several molecular events taking place. Peptide binding to biomaterial surfaces and interfaces under biological environments needs to be investigated in detail. Similarly, multi-domain activity of the peptides also requires significant exploration into in vitro and in vivo performances to ensure the robust multifunctional activities of the resultant molecular assemblies are maintained. Herein, we explored engineered peptide design incorporated with different bioactive domains to address unique biomedical challenges to investigate them as effective and robust multi-functional biomolecular assemblers for selected biomedical applications under conditions ranging from in vitro to in vivo environments. This hypothesis is supported by the inclusion of three publications, presented herein, where a variety of peptide-enabled biomolecular systems were studied as biohybrid technologies for different applications. These applications include: 1) Capturing bioactivity in polymer fiber mats toward the design of novel, tunable biomaterials. Here, bioactive shape memory polymer (SMP) fiber mats were developed as a self-assembled biohybrid material system. Nanofibers composed of poly(l-lactide)/poly(methyl methacrylate) (PLLA/PMMA) were produced using pressurized infusion gyration and incorporated a fusion fluorescence protein tagged with mineral binding peptide. Peptide-enabled design allowed for binding to hydroxyapatite nanoparticles as well as offered mineralization capability towards developing a tunable soft to hard material transition; 2) Imbalance of free biometal ions are recognized to play a critical role in neurodegenerative diseases. A peptide-enabled nanoprobe design was developed as a potential imaging tool to monitor free biometals associated with neurodegenerative diseases in a living zebrafish brain model with both spatial and temporal resolution; and 3) Caries is the most pervasive infectious disease of mankind and early childhood caries (ECC) and resultant destruction of the teeth is recognized as a global health crisis. Silver diamine fluoride (SDF) offers a promising treatment option but causes significant staining of caries-effected dental tissues. A peptide-enabled nanocomposite formation at the interface of SDF-treated dental tissues was developed. A novel bifunctional construct was developed, building upon the peptide binding ability to silver-stained dental tissues, to incorporate a peptide capable of mediated mineralization at this complex interface. The proposed approach offers the potential to overcome the black staining associated with the recently approved SDF caries arresting treatment. | |
