Acid-Base Equilibrium and Dielectric Environment Regulate Charge in Supramolecular Nanofibers

Abstract

Peptide amphiphiles are a class of molecules that can self-assemble into a variety of supramolecular structures, including high-aspect-ratio nanofibers. It is challenging to model and predict the charges in these supramolecular nanofibers because the ionization state of the peptides are not fixed but liable to change due to the acid-base equilibrium that is coupled to the structural organization of the peptide amphiphile molecules. Here, we have developed a theoretical model to describe and predict the amount of charge found on self-assembled peptide amphiphiles as a function of pH and ion concentration. In particular, we computed the amount of charge of peptide amphiphiles nanofibers with the sequence C16 − V2A2E2. In our theoretical formulation, we consider charge regulation of the carboxylic acid groups, which involves the acid-base chemical equilibrium of the glutamic acid residues and the possibility of ion condensation. The charge regulation is coupled with the local dielectric environment by allowing for a varying dielectric constant that also includes a position-dependent electrostatic solvation energy for the charged species. We find that the charges on the glutamic acid residues of the peptide amphiphile nanofiber are much lower than the same functional group in aqueous solution. There is a strong coupling between the charging via the acid-base equilibrium and the local dielectric environment. Our model predicts a much lower degree of deprotonation for a position-dependent relative dielectric constant compared to a constant dielectric background. Furthermore, the shape and size of the electrostatic potential as well as the counterion distribution are quantitatively and qualitatively different. These results indicate that an accurate model of peptide amphiphile self-assembly must take into account charge regulation of acidic groups through acid–base equilibria and ion condensation, as well as coupling to the local dielectric environment.

Aggregation-Induced Asymmetric Charge States of Amino Acids in Supramolecular Nanofibers

“…The results indicate that all-charged models might be oversimplified and inaccurate. That is, as found in previous studies of peptide assembly including continuum, coarse grained and/or all atom models, our results indicate that acid–base equilibrium should be considered in modeling PA supramolecular assembly systems.…”

“…Therefore, in these cases, regardless of the strong approximations, fully charged PA models often yield qualitative accurate results. 32 Another major reason lies in the deceiving fact that amino acids are calculated to be charged by using experimental pH and the theoretical pK a s of the amino acids. However, the pK a of an amino acid is a function of its surroundings 37 and can vary significantly.…”

“…Theorists have made efforts to predict the acid–base equilibrium between the protonated and deprotonated acids in PA self-assembly under different pH and salt conditions. − However, the phenomenon draw few attention in simulation works. , All amino acids are usually assumed to be charged if they have an acidic/basic side chain. The first reason is the computation expense in molecular dynamics (MD) simulations.…”

Influence of Membrane Permittivity on Charge Regulation of Weak Polyelectrolytes End-Tethered in Nanopores

“…Past calculations of planar polyelectrolyte brushes using a local dielectric constant, taken to be the linear volume-weighted average of the dielectric constant of water and the polymer, showed this to be a reasonable approximation for the low and intermediate density of polymer layers studied here. Only in very dense systems does the local dielectric environment appear to have a significant impact on charge regulation . Moreover, we assumed linear polarizability of the aqueous medium, which is an empirical description of the dielectric properties of the system.…”

Interplay of Polymer Structure, Solvent Ordering, and Charge Fluctuations in Polyelectrolyte Solution Thermodynamics

“…While there are numerous investigations into highly correlated charged systems, , dielectric inhomogeneities present an additional challenge. Commonly, solvent dielectric properties are assumed to be uniform across the polyelectrolyte solution. , However, nonuniform solvent polarization generated by local electric fields , is an important contributor to electrostatic correlations. − For example, dielectric constants are shown to vary from a low value of 5 neighboring the chain to approximately 80 in a bulk aqueous solution (i.e., water as the solvent) over a distance of 2 nm . In the strong coupling limit, the higher multipoles in the ionic network only contribute when there is dielectric inhomogeneity .…”