Investigation of peptide-mediated crystal habits using a high-content screening platform
Jun Ha Kwak, Felix Fan, Jeffrey D. Rimer, and Pankaj Karande
Crystals are prevalent in nature and heavily studied due to their versatility and impact in a wide range of fields. Examples of engineering crystal structures and properties range from tuning bioavailability of drugs to enhancing catalytic activities of zeolites. Biology excels at this by employing biomolecules (e.g. proteins) for the assembly of organic-inorganic hybrid materials (e.g. bones, teeth, shells). Proteins function as growth modifiers by adsorbing to crystal surfaces, altering anisotropic growth and, subsequently, producing distinct crystal habits. We are taking a bio-inspired approach to design peptides that mimic such proteins and effectively modify crystal growth and morphology. We developed a high-content screening assay that can rapidly mine optical microscopy images, quantify crystal shape factors, and determine the effects of peptides on crystallization. Lead peptides can be further investigated to elucidate the mechanisms of peptide-crystal interactions. We have tailored the assay for calcium oxalate monohydrate (COM), a major contributor to the kidney stone disease, and screened peptides derived from the calcium-binding protein, osteocalcin. We will present the various COM crystal habits induced by unique physicochemical properties of the peptides (e.g. charge density and secondary structure) and rationalize on the binding properties. COM is a model calcium-based system and enables our results to be applied in the design of peptides that control other forms of calcification. The work has further implications in the treatment of stone pathology and advanced materials processing.