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

Rikkert J. Nap; Baofu Qiao; Liam C. Palmer; Samuel I. Stupp; Monica Olvera de la Cruz; Igal Szleifer

doi:10.3389/fchem.2022.852164

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

Rikkert J. Nap^*, Baofu Qiao, Liam C. Palmer, Samuel I. Stupp, Monica Olvera de la Cruz, Igal Szleifer^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English (US)
Article number	852164
Journal	Frontiers in Chemistry
Volume	10
DOIs	https://doi.org/10.3389/fchem.2022.852164
State	Published - Mar 16 2022

Funding

RJN thanks Ivan R. Sasselli and Zois Syrgiannis for useful discussions. This research was supported in part through the computational resources and staff contributions provided for the Quest high performance computing facility at Northwestern University which is jointly supported by the Office of the Provost, the Office for Research, and Northwestern University Information Technology. This work was supported by the Center for Bio-Inspired Energy 1433 Science, an Energy Frontier Research Center funded by the U.S. 1434 Department of Energy (DOE), Office of Science, Basic Energy Sciences (BES), under Award # DE-SC0000989. Additional support for guidance and supervision of the project by IS was provided by the National Science Foundation, Div. of Chem. Bioeng. Env. and Transp. Sys. 1833214 (IS).

Keywords

charge regulation
dielectric constant
ion condensation
peptide amphiphiles
theory

ASJC Scopus subject areas

General Chemistry

Access to Document

10.3389/fchem.2022.852164

Cite this

@article{19eafe9063294a8ba3def80b3a546211,

title = "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.",

keywords = "charge regulation, dielectric constant, ion condensation, peptide amphiphiles, theory",

author = "Nap, {Rikkert J.} and Baofu Qiao and Palmer, {Liam C.} and Stupp, {Samuel I.} and {Olvera de la Cruz}, Monica and Igal Szleifer",

note = "Publisher Copyright: Copyright {\textcopyright} 2022 Nap, Qiao, Palmer, Stupp, Olvera de la Cruz and Szleifer.",

year = "2022",

month = mar,

day = "16",

doi = "10.3389/fchem.2022.852164",

language = "English (US)",

volume = "10",

journal = "Frontiers in Chemistry",

issn = "2296-2646",

publisher = "Frontiers Media SA",

}

TY - JOUR

T1 - Acid-Base Equilibrium and Dielectric Environment Regulate Charge in Supramolecular Nanofibers

AU - Nap, Rikkert J.

AU - Qiao, Baofu

AU - Palmer, Liam C.

AU - Stupp, Samuel I.

AU - Olvera de la Cruz, Monica

AU - Szleifer, Igal

PY - 2022/3/16

Y1 - 2022/3/16

N2 - 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.

AB - 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.

KW - charge regulation

KW - dielectric constant

KW - ion condensation

KW - peptide amphiphiles

KW - theory

UR - http://www.scopus.com/inward/record.url?scp=85127510822&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85127510822&partnerID=8YFLogxK

U2 - 10.3389/fchem.2022.852164

DO - 10.3389/fchem.2022.852164

M3 - Article

C2 - 35372273

AN - SCOPUS:85127510822

SN - 2296-2646

VL - 10

JO - Frontiers in Chemistry

JF - Frontiers in Chemistry

M1 - 852164

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this