Solid-Binding Peptides Enable Biomolecular Surface Assemblies and Mineralization

Abstract

The field of biomimicry spans many disciplines, with the common goal being to bring natural advances to modern technology. Understanding how organisms are capable of forming and modifying solids has been a fundamental question for decades. Organisms often utilize proteins in their interactions with inorganic materials. Despite many years of intense research, the key mechanism(s) of protein-mineral interactions and their pathways to mineralization still eludes us. Our lab’s research delves into genetically designing and engineering peptides that have an affinity for solids with the purpose of using them as molecular building blocks in materials synthesis, assembly, and formation. As part of developing these tools for biotechnology, solid-binding peptides found via several methods were used in a variety of proof-of-principle applications. The research herein encompasses: 1. Self-assembly of peptides on solid substrates; 2. Selection of peptides for distinct polymorphs and their biomineralization; and 3. Peptide-ion interactions, via solution processing and peptide-controlled biomineralization. The research was undertaken using an array of molecular biology, genetic engineering, materials science and engineering techniques and approaches. Selected peptide structures and solid interactions were studied using computational biology, molecular dynamics and bioinformatics, while the solid formation was studied using solution and gel biomineralization. In research 1, sequences have been rationally designed, based on self-assembled peptide (SAP) nanostructures on atomically flat surfaces, from an Alzheimer’s protein, Aβ, for assembly on a highly ordered pyrolytic graphite surface (HOPG) that mimic amyloid formation. Not only can this research advance technology, but it may also bring about a better understanding of protein fibrillation in neurodegenerative diseases. Research 2 was undertaken using the example of calcium carbonate, which is known to be a major biomineral constituent in shells of numerous mollusks. In this research a cell surface library was used to select peptides that bound to two polymorphs of CaCO3: calcite and aragonite. The genetically selected peptides were used to modify the polymorph and to understand possible functional domains of their biological counterparts. Finally in research 3, a biomineralizing soft-matter diffusion couple has been developed to control interface formation between two hard tissues mimicking the dentin-enamel junction (DEJ) in mammalian teeth containing hydroxyapatite (HAP). In all three cases, the peptides used are significantly shorter and simpler (7-18 amino acids) than their counterpart proteins in biology (100s of AAs long), but yet enabled material formation under controlled biological conditions of neutral pH in water at room temperature. A list of molecular biomimetic lessons learned from this study will have significant implications in future practical technologies.