Abstract

Extracellular matrix proteins of hard tissues are thought to play a key role in biomineralization , but whether other types of protein-derived biomolecules can promote the formation of mineralized crystals remains to be explored. Recent studies have shown that functional ultrashort peptides, which are less than seven amino acids in length, can partially replace the function of proteins and show unique physiological advantages. In this study, for the first time, we designed ultrashort peptides composed of several acid amino acids (serine and glutamic acid) based on the intrinsically disordered extracellular matrix proteins predicted by AlphaFold2 to explore new ideas for promoting the formation of hydroxyapatite crystals. We synthesized several ultrashort peptides with different amino acid combinations and lengths, such as SE and SESSE to evaluate the correlation between the sequence characteristics and biomineralization ability. The morphological characteristics of the crystals, cell adhesion with ultrashort peptides, and their role in tooth remineralization and bone formation were examined. In conclusion, ultrashort peptides can play an active role in the biomineralization in vivo and in vitro , which provides new insights into novel molecules that induce biomineralization and explores new therapeutic strategies for mineral loss.