Peptide binding motifs for calcium phosphate surfaces and their translation into synthetic copolymers

Abstract

The ability to address hydroxyapatite (HAp) surfaces with high affinity and specificity is key to many applications in areas like biomedicine, personal care or materials science. From both natural and engineered systems, it is well known that polycarboxylates such as poly(aspartic acid) interact strongly with HAp and can thus be used for efficient surface modification. However, the space of other chemical motifs for binding has hardly been explored and exploited so far. In this context, we have applied phage display (PD) to characterize HAp surfaces and obtain peptide sequences showing high affinity to HAp through evolutionary selection. Surprisingly, analyses of the obtained results and data from previous PD experiments on HAp reveal that the selected peptide sequences contain only minor amounts of amino acids with anionic groups (like aspartic acid) and are rather dominated by cationic, H-bonding and hydrophobic moieties. Based on this information, synthetic analogs were prepared through random copolymerization of acrylic monomers carrying similar functional groups in ratios predicted by phage display. Some of the resulting copolymers showed strong adsorption on hydroxyapatite on levels comparable to neat polycarboxylates. These findings demonstrate that alternative chemical motifs exist for targeting HAp surfaces, which may be leveraged for advanced control over interfacial processes in applied settings and could have implications for a better understanding of protein-mineral interactions in biological systems.