5 research outputs found
Molecular Dynamics Simulations of Polyelectrolyte Complexes
Polyelectrolyte
complexes (PECs) are currently of great interest
due to their applications toward developing new adaptive materials
and their relevance in membraneless organelles. These complexes emerge
during phase separation when oppositely charged polymers are mixed
in aqueous media. Peptide-based PECs are particularly useful toward
developing new drug delivery methods due to their inherent biocompatibility.
The underlying peptide sequence can be tuned to optimize specific
material properties of the complex, such as interfacial tension and
viscosity. Given their applicability, it would be advantageous to
understand the underlying sequence-dependent phase behavior of oppositely
charged peptides. Here, we report microsecond molecular dynamic simulations
to characterize the effect of hydrophobicity on the sequence-dependent
peptide conformation for model polypeptide sequences that were previously
reported by Tabandeh et al. These sequences are designed
with alternating chirality of the peptide backbone. We present microsecond
simulations of six oppositely charged peptide pairs, characterizing
the sequence-dependent effect on peptide size, degree of hydrogen
bonding, secondary structure, and conformation. This analysis recapitulates
sensible trends in peptide conformation and degree of hydrogen bonding,
consistent with experimentally reported results. Ramachandran plots
reveal that backbone conformation at the single amino acid level is
highly influenced by the neighboring sequence in the chain. These
results give insight into how subtle changes in hydrophobic side chain
size and chirality influence the strength of hydrogen bonding between
the chains and, ultimately, the secondary structure. Furthermore,
principal component analysis reveals that the minimum energy structures
may be subtly modulated by the underlying sequence
OligonucleotideâPeptide Complexes: Phase Control by Hybridization
When oppositely charged polymers
are mixed, counterion release
drives phase separation; understanding this process is a key unsolved
problem in polymer science and biophysical chemistry, particularly
for nucleic acids, polyanions whose biological functions are intimately
related to their high charge density. In the cell, complexation by
basic proteins condenses DNA into chromatin, and membraneless organelles
formed by liquidâliquid phase separation of RNA and proteins
perform vital functions and have been linked to disease. Electrostatic
interactions are also the primary method used for assembly of nanoparticles
to deliver therapeutic nucleic acids into cells. This work describes
complexation experiments with oligonucleotides and cationic peptides
spanning a wide range of polymer lengths, concentrations, and structures,
including RNA and methylphosphonate backbones. We find that the phase
of the complexes is controlled by the hybridization state of the nucleic
acid, with double-stranded nucleic acids forming solid precipitates
while single-stranded oligonucleotides form liquid coacervates, apparently
due to their lower charge density. Adding salt âmeltsâ
precipitates into coacervates, and oligonucleotides in coacervates
remain competent for sequence-specific hybridization and phase change,
suggesting the possibility of environmentally responsive complexes
and nanoparticles for therapeutic or sensing applications
OligonucleotideâPeptide Complexes: Phase Control by Hybridization
When oppositely charged polymers
are mixed, counterion release
drives phase separation; understanding this process is a key unsolved
problem in polymer science and biophysical chemistry, particularly
for nucleic acids, polyanions whose biological functions are intimately
related to their high charge density. In the cell, complexation by
basic proteins condenses DNA into chromatin, and membraneless organelles
formed by liquidâliquid phase separation of RNA and proteins
perform vital functions and have been linked to disease. Electrostatic
interactions are also the primary method used for assembly of nanoparticles
to deliver therapeutic nucleic acids into cells. This work describes
complexation experiments with oligonucleotides and cationic peptides
spanning a wide range of polymer lengths, concentrations, and structures,
including RNA and methylphosphonate backbones. We find that the phase
of the complexes is controlled by the hybridization state of the nucleic
acid, with double-stranded nucleic acids forming solid precipitates
while single-stranded oligonucleotides form liquid coacervates, apparently
due to their lower charge density. Adding salt âmeltsâ
precipitates into coacervates, and oligonucleotides in coacervates
remain competent for sequence-specific hybridization and phase change,
suggesting the possibility of environmentally responsive complexes
and nanoparticles for therapeutic or sensing applications
Ternary, Tunable Polyelectrolyte Complex Fluids Driven by Complex Coacervation
Complex coacervation was achieved
by combining polyÂ(allylamine)
(PAH) or branched polyÂ(ethylenimine) (PEI) with polyÂ(acrylic acid)
(PAA) and polyÂ(<i><i>N,N</i></i>-dimethylaminoethyl
methacrylate) (PDMAEMA). We systematically investigated the effects
of stoichiometry, salt concentration, and pH. Ternary coacervates
formed over a broader range of stoichiometries compared to the base
PAA/PDMAEMA system. An enhanced resistance to salt, that is, resistance
to dissolution of the complex with added salt, was observed for ternary
coacervates. PEI-containing systems showed a considerable difference
in salt resistance at pH 6â8 due to the dramatic change in
charge density. This change was interpreted in the context of a theoretical
treatment that relies on the VoornâOverbeek model for free
energy. Coacervate stability and viscoelastic behavior were affected
by stoichiometry, salt, and pH. Ternary coacervates maintain the characteristics
and tunability of typical binary coacervates, but the choice of the
third component is important, as it significantly affects the response
and material properties
Interfacial Tension of Polyelectrolyte Complex Coacervate Phases
We
consider polyelectrolyte solutions which, under suitable conditions,
phase separate into a liquid-like coacervate phase and a coexisting
supernatant phase that exhibit an extremely low interfacial tension.
Such interfacial tension provides the basis for most coacervate-based
applications, but little is known about it, including its dependence
on molecular weight, charge density, and salt concentration. By combining
a DebyeâHuÌckel treatment for electrostatic interactions
with the CahnâHilliard theory, we derive explicit expressions
for this interfacial tension. In the absence of added salts, we find
that the interfacial tension scales as <i>N</i><sup>â3/2</sup>(η/η<sub>c</sub>â1)<sup>3/2</sup> near the critical
point of the demixing transition, and that it scales as η<sup>1/2</sup> far away from it, where <i>N</i> is the chain
length and η measures the electrostatic interaction strength
as a function of temperature, dielectric constant, and charge density
of the polyelectrolytes. For the case with added salts, we find that
the interfacial tension scales with the salt concentration Ï
as <i>N</i><sup>â1/4</sup>(1âÏ/Ï<sub>c</sub>)<sup>3/2</sup> near the critical salt concentration Ï<sub>c</sub>. Our predictions are shown to be in quantitative agreement
with experiments and provide a means to design new materials based
on polyelectrolyte complexation