Morphology and aggregation of RADA-16-I peptide Studied by AFM, NMR and molecular dynamics simulations.
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.
Scientific Research Institute of Physical-Chemical Medicine, Malaya Pirogovskaya, 1a Moscow, 119435, Russian Federation.|Faculty of Biology, Department of Bioengineering, M.V. Lomonosov Moscow State University, Leninskie Gory, 1/73, Moscow, 111991, Russian Federation.
Dmitry
D
Bagrov
Scientific Research Institute of Physical-Chemical Medicine, Malaya Pirogovskaya, 1a Moscow, 119435, Russian Federation.|Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, Institutsky Lane 9, Dolgoprudny, Moscow Region, 141700, Russian Federation.
Yuliya
Y
Gazizova
Scientific Research Institute of Physical-Chemical Medicine, Malaya Pirogovskaya, 1a Moscow, 119435, Russian Federation.
Victor
V
Podgorsky
Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Prospect Nauki-6, Pushchino, 142290, Russian Federation.|Pushchino State Institute of Natural Science, Prospect Nauki-3, Pushchino, 142290, Russian Federation.
Igor
I
Udovichenko
Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Prospect Nauki-6, Pushchino, 142290, Russian Federation.|Pushchino State Institute of Natural Science, Prospect Nauki-3, Pushchino, 142290, Russian Federation.
Alexey
A
Danilkovich
Scientific Research Institute of Physical-Chemical Medicine, Malaya Pirogovskaya, 1a Moscow, 119435, Russian Federation.
Kirill
K
Prusakov
Scientific Research Institute of Physical-Chemical Medicine, Malaya Pirogovskaya, 1a Moscow, 119435, Russian Federation.|Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya, 16/10, Moscow, 117997, Russian Federation.
Dmitry
D
Klinov
D018625:Microscopy, Atomic Force / Q000379:methods*; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010455:Peptides / Q000737:chemistry*
D010455:Peptides; C546681:RADA16-I
RADA-16-I peptide; amyloid-like fibrils; atomic-force microscopy; nuclear magnetic resonance; peptide monolayer