Using Molecular Dynamics to Study Liquid Phase Behavior: Simulations of the Ternary Sodium Laurate/Sodium Oleate/Water System

King, Dylan T; Warren, Dallas; Pouton, Colin W.; Chalmers, David K.

doi:10.1021/la2022903

Cited by 36 publications

(45 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13 MD simulations have also been applied to study the self-assembly of ionized fatty acids, such as octanoate (C8 fatty acid) 14 and laurate (C12 fatty acid) as well as oleate (C18 fatty acid with a double bond). 15 One aspect that has been missing in all simulation work published so far (except for our recent work, 16 see below) is the effect of pH, which, as discussed earlier, plays an important role in controlling the phase and morphological behavior of ionizable surfactants. To mimic the change in pH, one approach is to run multiple simulations with varying ratios of protonated and deprotonated molecules.…”

Section: Introductionmentioning

confidence: 93%

Self-Assembly and Bilayer–Micelle Transition of Fatty Acids Studied by Replica-Exchange Constant pH Molecular Dynamics

2013

View full text Add to dashboard Cite

Recent interest in the development of surfactant-based nano delivery systems targeting tumor sites has sparked our curiosity to understand the detailed mechanism of the self-assembly and phase transitions of pH-sensitive surfactants. Towards this goal we applied a state-of-the-art simulation technique, continuous constant pH molecular dynamics (CpHMD) with the hybrid-solvent scheme and pH-based replica-exchange protocol, to study de novo self-assembly of 30 and 40 lauric acids, a simple model titratable surfactant. We observed the formation of a gel-state bilayer at low and intermediate pH and a spherical micelle at high pH, with the phase transition starting at 20–30% ionization and completing at 50%. The degree of cooperativity for the transition increases from the 30-mer to the 40-mer. The calculated apparent or bulk pKa value is 7.0 for the 30-mer and 7.5 for the 40-mer. Congruent with experiment, these data demonstrate that CpHMD is capable of accurately modeling large conformational transitions of surfactant systems while allowing simultaneous proton titration of constituent molecules. We suggest that CpHMD simulations may become a useful tool to aid in the design and development of pH-sensitive nanocarriers for a variety of biomedical and technological applications.

show abstract

Section: Introductionmentioning

confidence: 93%

Self-Assembly and Bilayer–Micelle Transition of Fatty Acids Studied by Replica-Exchange Constant pH Molecular Dynamics

2013

View full text Add to dashboard Cite

show abstract

“…20 Oleate self-aggregation was simulated at a number of different concentrations, although without any neutral oleic acid. 21 Oleic acid triple layers were studied with atomistic simulations, finding fast diffusion of monomers across the aggregate, although oleate was not included in this system. 22 Morrow and co-workers investigated small lauric acid aggregates using constant pH simulations with atomistic models, showing a positive shift in the pK a in aggregates.…”

Section: ■ Introductionmentioning

confidence: 99%

Oleic Acid Phase Behavior from Molecular Dynamics Simulations

2014

View full text Add to dashboard Cite

Fatty acid aggregation is important for a number of diverse applications: from origins of life research to industrial applications to health and disease. Experiments have characterized the phase behavior of oleic acid mixtures, but the molecular details are complex and hard to probe with many experiments. Coarse-grained molecular dynamics computer simulations and free energy calculations are used to model oleic acid aggregation. From random dispersions, we observe the aggregation of oleic acid monomers into micelles, vesicles, and oil phases, depending on the protonation state of the oleic acid head groups. Worm-like micelles are observed when all the oleic acid molecules are deprotonated and negatively charged. Vesicles form spontaneously if significant amounts of both neutral and negative oleic acid are present. Oil phases form when all the fatty acids are protonated and neutral. This behavior qualitatively matches experimental observations of oleic acid aggregation. To explain the observed phase behavior, we use umbrella sampling free energy calculations to determine the stability of individual monomers in aggregates compared to water. We find that both neutral and negative oleic acid molecules prefer larger aggregates, but neutral monomers prefer negatively charged aggregates and negative monomers prefer neutral aggregates. Both neutral and negative monomers are most stable in a DOPC bilayer, with implications on fatty acid adsorption and cellular membrane evolution. Although the CG model qualitatively reproduces oleic acid phase behavior, we show that an updated polarizable water model is needed to more accurately predict the shift in pKa for oleic acid in model bilayers.

show abstract

“…7 With the explosion of computing power, molecular dynamics simulations are becoming an increasingly valuable tool for elucidating microscopic mechanisms of surfactant assembly and phase behavior that are difficult or impossible to obtain using wet-lab experiments. [8][9][10] Until now all simulations have been conducted based on fixed protonation states. The effect of solution pH has not been explored in a satisfactory manner.…”

Section: Introductionmentioning

confidence: 99%

Atomistic simulations of pH-dependent self-assembly of micelle and bilayer from fatty acids

Morrow

Koenig

Shen

2012

The Journal of Chemical Physics

View full text Add to dashboard Cite

Detailed knowledge of the self-assembly and phase behavior of pH-sensitive surfactants has implications in areas such as targeted drug delivery. Here we present a study of the formation of micelle and bilayer from lauric acids using a state-of-the-art simulation technique, continuous constant pH molecular dynamics (CpHMD) with conformational sampling in explicit solvent and the pH-based replica-exchange protocol. We find that at high pH conditions a spherical micelle is formed, while at low pH conditions a bilayer is formed with a considerable degree of interdigitation. The mid-point of the phase transition is in good agreement with experiment. Preliminary investigation also reveals that the effect of counterions and salt screening shifts the transition mid-point and does not change the structure of the surfactant assembly. Based on these data we suggest that CpHMD simulations may be applied to computational design of surfactant-based nano devices in the future.

show abstract

Using Molecular Dynamics to Study Liquid Phase Behavior: Simulations of the Ternary Sodium Laurate/Sodium Oleate/Water System

Cited by 36 publications

References 57 publications

Self-Assembly and Bilayer–Micelle Transition of Fatty Acids Studied by Replica-Exchange Constant pH Molecular Dynamics

Self-Assembly and Bilayer–Micelle Transition of Fatty Acids Studied by Replica-Exchange Constant pH Molecular Dynamics

Oleic Acid Phase Behavior from Molecular Dynamics Simulations

Atomistic simulations of pH-dependent self-assembly of micelle and bilayer from fatty acids

Contact Info

Product

Resources

About