The mechanism underlying self-assembly of short peptides has not been fully understood despite the fact that a few decades have passed since their serendipitous discovery. RADA16-I (AcN-RADARADARADARADA-CONH2), representative of a class of self-assembling peptides with alternate hydrophobic and hydrophilic residues, self-assembles into β-sheet bilayer filaments. Though a sliding diffusion model for this class of peptides has been developed in previous works, this theory need further improvements, supported by experimental investigations, to explain how RADA16-I functionalization with biological active motifs, added at the C-terminus of the self-assembling core sequence, may influence the self-assembling tendency of new functionalized peptides (FPs). Since FPs recently became a promising class of biomaterials for cell biology and tissue engineering, a better understanding of the phenomenon is necessary to design new scaffolds for nanotechnology applications. In this work we investigated via atomic force microscopy and Raman spectroscopy the assembly of three RADA16-I FPs that have different hydrophobic/hydrophilic profiles and charge distributions. We performed molecular dynamics simulations to provide further insights into the experimental results: functionalizing self-assembling peptides can strongly influence or prevent molecular assembly into nanofibers. We also found certain vibrational molecular modes in Raman spectroscopy to be useful indicators for elucidating the assembly propensity of FPs. Preliminary FP designing strategies should therefore include functional motif sequences with balanced hydrophobicity profiles avoiding hydrophobic patches, causing fast hydrophobic collapses of the FP molecules, or very hydrophilic motifs capable of destabilizing the RADA16-I double layered β-sheet structure.
ASJC Scopus subject areas
- Condensed Matter Physics