20 research outputs found
Competing interactions in two dimensional Coulomb systems: Surface charge heterogeneities in co-assembled cationic-anionic incompatible mixtures
A binary mixture of oppositely charged components confined to a plane such as
cationic and anionic lipid bilayers may exhibit local segregation. The relative
strength of the net short range interactions, which favors macroscopic
segregation, and the long range electrostatic interactions, which favors
mixing, determines the length scale of the finite size or microphase
segregation. The free energy of the system can be examined analytically in two
separate regimes, when considering small density fluctuations at high
temperatures, and when considering the periodic ordering of the system at low
temperatures (F. J. Solis and M. Olvera de la Cruz, J. Chem. Phys. 122, 054905
(2000)). A simple Molecular Dynamics simulation of oppositely charged monomers,
interacting with a short range Lennard Jones potential and confined to a two
dimensional plane, is examined at different strengths of short and long range
interactions. The system exhibits well-defined domains that can be
characterized by their periodic length-scale as well as the orientational
ordering of their interfaces. By adding salt, the ordering of the domains
disappears and the mixture macroscopically phase segregates in agreement with
analytical predictions.Comment: 8 pages, 5 figures, accepted for publication in J. Chem. Phys, Figure
1 include
Charged Particles on Surfaces: Coexistence of Dilute Phases and Periodic Structures on Membranes
We consider a mixture of one neutral and two oppositely charged types of
molecules confined to a surface. Using analytical techniques and molecular
dynamics simulations, we construct the phase diagram of the system and exhibit
the coexistence between a patterned solid phase and a charge-dilute phase. The
patterns in the solid phase arise from competition between short-range
immiscibility and long-range electrostatic attractions between the charged
species. The coexistence between phases leads to observations of stable
patterned domains immersed in a neutral matrix background.Comment: 5 pages, 3 figure
Curvature-driven Molecular Demixing in the Budding and Breakup of Mixed Component Worm-like Miscelles
Amphiphilic block copolymers of suitable proportions can self-assemble into surprisingly long and stable worm-like micelles, but the intrinsic polydispersity of polymers as well as polymer blending efforts and the increasing use of degradable chains all raise basic questions of curvature–composition coupling and morphological stability of these high curvature assemblies. Molecular simulations here of polyethylene glycol (PEG) based systems show that a systematic increase in the hydrated PEG fraction, in both monodisperse and binary blends, induces budding and breakup into spherical and novel ‘dumbbell’ micelles—as seen in electron microscopy images of degradable worm-like micelles. Core dimension, d, in our large-scale, long-time dissipative particle dynamics (DPD) simulations is shown to scale with chain-length, N, as predicted theoretically by the strong segregation limit (d ≈ N2/3), but morphological transitions of binary mixtures are only crudely predicted by simple mixture rules. Here we show that for weakly demixing diblock copolymers, the coupling between local interfacial concentration and mean curvature can be described with a simple linear relationship. The computational methods developed here for PEG-based assemblies should be useful for many high curvature nanosystems
Characterisation of the hydrophobic collapse of polystyrene in water using free energy techniques
<p>We characterise the hydrophobic collapse of single polystyrene chains in water using molecular dynamics simulations. Specifically, we calculate the potential of mean force for the collapse of a single polystyrene chain in water using metadynamics, comparing the results between all atomistic with coarse-grained (CG) molecular simulation. We next explore the scaling behaviour of the collapsed globular shape at the minimum energy configuration, characterised by the radius of gyration, as a function of chain length. The exponent is close to one third, consistent with that predicted for a polymer chain in bad solvent. We also explore the scaling behaviour of the solvent accessible surface area (SASA) as a function of chain length, finding a similar exponent for both all atomistic and CG simulations. Furthermore, calculation of the local water density as a function of chain length near the minimum energy configuration suggests that intermediate chain lengths are more likely to form dewetted states, as compared to shorter or longer chain lengths.</p
Molecular dynamics simulations of the interaction of phospholipid bilayers with polycaprolactone
Molecular Simulation of the Concentration-Dependent Interaction of Hydrophobic Drugs with Model Cellular Membranes
We report here the interactions between
a hydrophobic drug and
a model cellular membrane at the molecular level using all-atom molecular
dynamics simulations of paclitaxel, a hydrophobic cancer drug. The
calculated free energy of a single drug across the bilayer interface
displays a minimum in the outer hydrophobic zone of the membrane.
The transfer free energy shows excellent agreement with reported experimental
data. In two sets of long-time simulations of high concentrations
of drug in the membrane (12 and 11 mol %), the drugs display substantial
clustering and rotation with significant directional preference in
their diffusion. The main taxane ring partitions in the outer hydrophobic
zone, while the three phenyl rings prefer to be closer to the hydrophobic
core of the membrane. The clustering of the drug molecules, order
parameters of the lipid tails, and water penetration suggest that
the fluidity and permeability of the membrane are affected by the
concentration of drugs that it contains. Furthermore, at the high-concentration
limit, the free energy minimum shifts closer to the hydrophobic core
and the central barrier to cross the membrane decreases. Moreover,
the transfer free energy change substantially increases, suggesting
that increasing concentration facilitates drug partitioning into the
membrane
Molecular Dynamics Simulations of Supramolecular Anticancer Nanotubes
We
report here on long-time all-atomistic molecular dynamics simulations
of functional supramolecular nanotubes composed by the self-assembly
of peptide-drug amphiphiles (DAs). These DAs have been shown to possess
an inherently high drug loading of the hydrophobic anticancer drug
camptothecin. We probe the self-assembly mechanism from random with
∼0.4 μs molecular dynamics simulations. Furthermore,
we also computationally characterize the interfacial structure, directionality
of π–π stacking, and water dynamics within several
peptide-drug nanotubes with diameters consistent with the reported
experimental nanotube diameter. Insight gained should inform the future
design of these novel anticancer drug delivery systems
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
π–π Stacking Mediated Chirality in Functional Supramolecular Filaments
While a great diversity of peptide-based
supramolecular filaments
have been reported, the impact of an auxiliary segment on the chiral
assembly of peptides remains poorly understood. Herein we report on
the formation of chiral filaments by the self-assembly of a peptide-drug
conjugate containing an aromatic drug camptothecin (CPT) in a computational
study. We find that the chirality of the filament is mediated by the
π–π stacking between CPTs, not only by the well-expected
intermolecular hydrogen bonding between peptide segments. Our simulations
show that π–π stacking of CPTs governs the early
stages of the self-assembly process, while a hydrogen bonding network
starts at a relatively later stage to contribute to the eventual morphology
of the filament. Our results also show the possible presence of water
within the core of the CPT filament. These results provide very useful
guiding principles for the rational design of supramolecular assemblies
of peptide conjugates with aromatic segments