Effects of temperature, pH and counterions on the stability of peptide amphiphile nanofiber structures

Abstract

Peptide amphiphiles are a class of self-assembling molecules that are widely used to form bioactive nanostructures for various applications in bionanomedicine. However, peptide molecules can exhibit distinct behaviors under different conditions, suggesting that environmental variables such as temperature, pH, electrolytes and the presence of biological factors may greatly affect the self-assembly process. In this work, we used united-atom molecular dynamics simulations to understand the effects of three counterions (Na + , Ca 2+ at pH 7 and Cl À at pH 2) and temperature change on the stability of the lauryl-VVAGERGD peptide amphiphile self-assembly. This molecule contains a bioactive RGD peptide sequence and has been shown to support cellular adhesion and proliferation in vitro. A 19-layered peptide nanostructure, containing 12 peptide amphiphile molecules per layer, was previously shown to exhibit optimal stability and it was used as the model nanofiber system. Peptide backbone stability was studied under increasing temperatures (300-358 K) using the number of hydrogen bonds and rootmean-square deviations of nanofiber size. At higher temperatures, fiber disintegration was observed to be dependent on the type of counter-ion used for nanofiber formation. Interestingly, rapid heating to higher temperatures could sometimes reestablish the integrity of the nanofiber backbone, possibly by allowing the system to bypass an energy barrier and assuming a more thermodynamically stable configuration. As counterion identity was observed to exhibit remarkable effects on the thermal stability of peptide nanofibers, we suggest that these behaviors should be considered while developing new materials for potential applications. † Electronic supplementary information (ESI) available: Observations on PA1 nanober structure under extended simulation periods, secondary structure and radius of gyration analyses of all three PA congurations, and hydrogen bond formation of PA2 nanobers. See

SAPdb: A database of nanostructures formed by self-assembly of short peptides

“…Previous studies have shown that the variation in experimental conditions like the type of solvent, change in concentration of peptide, temperature, incubation time, pH, etc. can lead to the formation of different nanostructures by the same peptide [67]. Further, our analysis shows that the concentration of peptide is also an important factor for controlling the shape and size of the nanostructure.…”

Molecular simulations of peptide amphiphiles

“…As shown in Figure 4B, the disintegration temperature for the PA being simulated at pH 7 with Na + counterions is 358K. 30 Recent studies by Chen et al 84 and Cote et al . 26 reported under pH levels with low electrostatic repulsion, hydrogen bond formation between peptide segments is facilitated, disturbing the spherical micelle and forming the cylindrical nanofiber.…”

“…Disassembly was observed to occur at 358K. Adapted from ref 30 by permission of The Royal Society of Chemistry.…”

“…For example, electrostatic interactions between PA monomers can also be tuned through varying the pH of the solvent through the protonation and deprotonation of carboxylate or ammonium groups of peptide side chains. 30 Recently, Tantakitti et al . 40 showed that the contour length and mechanical stability of the PA filament can be tuned by varying the salt concentration.…”

Effect of Substrate Ratios and the Species of Sugar on the Antioxidant Activity of Glycosylated Products of the Rana Debris Collagen Peptide

“…A peptide has been enzymatically hydrolyzed from the Rana debris for use in research. The structure and functional characteristics of this peptide are easily destroyed because it is susceptible to pH [2], temperature [3], and other environmental effects [4], which limits the industrial use of the peptide.…”