Mucins play diverse and crucial roles in the body.  These functions range from lubrication of articular joints and the eye, to protection of stomach endothelium, to modulation of oral and gut microflora populations. Despite their diversity, these functions commonly stem from modifications in a general structure shared by all mucins: a blocky polypeptide backbone comprised of terminal moieties for binding surfaces or crosslinking and a characteristic glycosylated bottlebrush. <br/>Inspired by this adaptable structure, we have created a mucin analogue platform which engenders key structural features preserved among native mucins.  We have emulated the mucinous bottlebrush with a lysine-rich elastin-like polypeptide backbone, which provides primary amines for conjugation of synthetic polymer “bristles.”  Binding modules target surfaces of interest, to facilitate intramolecular associations, or to direct surface conformation of our construct.  <br/>            To demonstrate the application of our platform to clinically-relevant problems, we have tailored our mucin analogues to osteoarthritis and kidney stone disease, conditions infamous for profound morbidity and high prevalence. We will demonstrate that collagen-targeted mucin analogues adsorb to model surfaces and prevent protein fouling. This recapitulates the function of lubricin, a mucin downregulated in osteoarthritis. Similarly, we will show that we can target mineral surfaces relevant in kidney stone disease by exchanging the binding module of our analogue mucins. We will show that these altered analogues also inhibit protein-fouling, which is implicated in stone growth. In this platform technology, we have been inspired by the diverse functions of native mucins.  By harnessing the general structure which gives rise to these properties, we hope not only to replicate the <i>in vivo</i> function of mucins, but also to harness the properties of natural mucins and apply them to systems not naturally protected by mucinous coatings, such as inhibiting the growth of kidney stones.

Bio-inspired peptide-polymer hybrid mucin analogues: Applications in osteoarthritis and kidney stone disease

2019 Spring National Meeting

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