Morphology and aggregation of RADA-16-I peptide Studied by AFM, NMR and molecular dynamics simulations

• Published in: Biopolymers 2016-01, Vol.106 (1), p.72-81
• Main Authors: Bagrov, Dmitry, Gazizova, Yuliya, Podgorsky, Victor, Udovichenko, Igor, Danilkovich, Alexey, Prusakov, Kirill, Klinov, Dmitry
• Format: Article
• Language: English
• Subjects: amyloid-like fibrils; Atomic force microscopy; Biopolymers; Microscopy, Atomic Force - methods; Molecular dynamics; Molecular Dynamics Simulation; Monolayers; Morphology; nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular - methods; peptide monolayer; Peptides; Peptides - chemistry; RADA-16-I peptide; Simulation
• ISSN: 0006-3525; 1097-0282
• DOI: 10.1002/bip.22755

ABSTRACT RADA‐16‐I is a self‐assembling peptide which forms biocompatible fibrils and hydrogels. We used molecular dynamics simulations, atomic‐force microscopy, NMR spectroscopy, and thioflavin T binding assay to examine size, structure, and morphology of RADA‐16‐I aggregates. We used the native form of RADA‐16‐I (H‐(ArgAlaAspAla)4‐OH) rather than the acetylated one commonly used in the previous studies. At neutral pH, RADA‐16‐I is mainly in the fibrillar form, the fibrils consist of an even number of stacked β‐sheets. At acidic pH, RADA‐16‐I fibrils disassemble into monomers, which form an amorphous monolayer on graphite and monolayer lamellae on mica. RADA‐16‐I fibrils were compared with the fibrils of a similar peptide RLDL‐16‐I. Thickness of β‐sheets measured by AFM was in excellent agreement with the molecular dynamics simulations. A pair of RLDL‐16‐I β‐sheets was thicker (2.3 ± 0.4 nm) than a pair of RADA‐16‐I β‐sheets (1.9 ± 0.1 nm) due to the volume difference between alanine and leucine residues. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 72–81, 2016.