TY - JOUR
T1 - Effect of functionalization on the self-assembling propensity of β-sheet forming peptides
AU - Taraballi, Francesca
AU - Campione, Marcello
AU - Sassella, Adele
AU - Vescovi, Angelo
AU - Paleari, Alberto
AU - Hwang, Wonmuk
AU - Gelain, Fabrizio
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1039/b809236b
DO - 10.1039/b809236b
M3 - Article
AN - SCOPUS:67649998195
SN - 1744-683X
VL - 5
SP - 660
EP - 668
JO - Soft Matter
JF - Soft Matter
IS - 3
ER -