Tuning 尾-Sheet Peptide Self-Assembly and Hydrogelation Behavior by Modification of Sequence Hydrophobicity and Aromaticity

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• 作者：Charles J. Bowerman ; Wathsala Liyanage ; Alexander J. Federation ; Bradley L. Nilsson
• 刊名：Biomacromolecules
• 出版年：2011
• 出版时间：July 11, 2011
• 年：2011
• 卷：12
• 期：7
• 页码：2735-2745
• 全文大小：1270K
• 年卷期：v.12,no.7(July 11, 2011)
• ISSN：1526-4602

文摘

Peptide self-assembly leading to cross-尾 amyloid structures is a widely studied phenomenon because of its role in amyloid pathology and the exploitation of amyloid as a functional biomaterial. The self-assembly process is governed by hydrogen bonding, hydrophobic, aromatic 蟺鈥撓€, and electrostatic Coulombic interactions. A role for aromatic 蟺鈥撓€ interactions in peptide self-assembly leading to amyloid has been proposed, but the relative contributions of 蟺鈥撓€ versus general hydrophobic interactions in these processes are poorly understood. The Ac-(XKXK)₂-NH₂ peptide was used to study the contributions of aromatic and hydrophobic interactions to peptide self-assembly. Position X was globally replaced by valine (Val), isoleucine (Ile), phenylalanine (Phe), pentafluorophenylalanine (F₅鈥揚he), and cyclohexylalanine (Cha). At low pH, these peptides remain monomeric because of repulsion of charged lysine (Lys) residues. Increasing the solvent ionic strength to shield repulsive charge鈥揷harge interactions between protonated Lys residues facilitated cross-尾 fibril formation. It was generally found that as peptide hydrophobicity increased, the required ionic strength to induce self-assembly decreased. At [NaCl] ranging from 0 to 1000 mM, the Val sequence failed to assemble. Assembly of the Phe sequence commenced at 700 mM NaCl and at 300 mM NaCl for the less hydrophobic Ile variant, even though it displayed a mixture of random coil and 尾-sheet secondary structures over all NaCl concentrations. 尾-Sheet formation for F₅鈥揚he and Cha sequences was observed at only 20 and 60 mM NaCl, respectively. Whereas self-assembly propensity generally correlated to peptide hydrophobicity and not aromatic character the presence of aromatic amino acids imparted unique properties to fibrils derived from these peptides. Nonaromatic peptides formed fibrils of 3鈥?5 nm in diameter, whereas aromatic peptides formed nanotape or nanoribbon architectures of 3鈥? nm widths. In addition, all peptides formed fibrillar hydrogels at sufficient peptide concentrations, but nonaromatic peptides formed weak gels, whereas aromatic peptides formed rigid gels. These findings clarify the influence of aromatic amino acids on peptide self-assembly processes and illuminate design principles for the inclusion of aromatic amino acids in amyloid-derived biomaterials.