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A Permeability Study of O2 and the Trace Amine p-Tyramine through Model Phosphatidylcholine Bilayers.

ABSTRACT: We study here the permeability of the hydrophobic O2 molecule through a model DPPC bilayer at 323K and 350K, and of the trace amine p-tyramine through PC bilayers at 310K. The tyramine results are compared to previous experimental work at 298K. Nonequilibrium work methods were used in conjunction to simultaneously obtain both the potential of mean force (PMF) and the position dependent transmembrane diffusion coefficient, D(z), from the simulations. These in turn were used to calculate the permeability coefficient, P, through the inhomogeneous solubility-diffusion model. The results for O2 are consistent with previous simulations, and agree with experimentally measured P values for PC bilayers. A temperature dependence in the permeability of O2 through DPPC was obtained, with P decreasing at higher temperatures. Two relevant species of p-tyramine were simulated, from which the PMF and D(z) were calculated. The charged species had a large energetic barrier to crossing the bilayer of ~ 21 kcal/mol, while the uncharged, deprotonated species had a much lower barrier of ~ 7 kcal/mol. The effective in silico permeability for p-tyramine was calculated by applying three approximations, all of which gave nearly identical results (presented here as a function of the pKa). As the permeability value calculated from simulation was highly dependent on the pKa of the amine group, a further pKa study was performed that also varied the fraction of the uncharged and zwitterionic p-tyramine species. Using the experimental P value together with the simulated results, we were able to label the phenolic group as responsible for the pKa1 and the amine for the pKa2, that together represent all of the experimentally measured pKa values for p-tyramine. This agrees with older experimental results, in contrast to more recent work that has suggested there is a strong ambiguity in the pKa values.

SUBMITTER: Holland BW

PROVIDER: S-EPMC4472697 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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A Permeability Study of O2 and the Trace Amine p-Tyramine through Model Phosphatidylcholine Bilayers.

Holland Bryan W BW Berry Mark D MD Gray C G CG Tomberli Bruno B

PloS one 20150618 6

We study here the permeability of the hydrophobic O2 molecule through a model DPPC bilayer at 323K and 350K, and of the trace amine p-tyramine through PC bilayers at 310K. The tyramine results are compared to previous experimental work at 298K. Nonequilibrium work methods were used in conjunction to simultaneously obtain both the potential of mean force (PMF) and the position dependent transmembrane diffusion coefficient, D(z), from the simulations. These in turn were used to calculate the perme ...[more]

PMID: 26086933

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Project description:The mode of interactions between palmitoyl lysophosphatidylcholine (palmitoyl lyso-PC) or other lysophospholipids (lyso-PLs) and palmitoyl ceramide (PCer) or other ceramide analogs in dioleoylphosphatidylcholine (DOPC) bilayers has been examined. PCer is known to segregate laterally into a ceramide-rich phase at concentrations that depend on the nature of the ceramides and the co-phospholipids. In DOPC bilayers, PCer forms a ceramide-rich phase at concentrations above 10 mol%. In the presence of 20 mol% palmitoyl lyso-PC in the DOPC bilayer, the lateral segregation of PCer was markedly facilitated (segregation at lower PCer concentrations). The thermostability of the PCer-rich phase in the presence of palmitoyl lyso-PC was also increased compared to that in the absence of palmitoyl lyso-PC. Other saturated lyso-PLs (e.g., palmitoyl lyso-phosphatidylethanolamine and lyso-sphingomyelin) also facilitated the lateral segregation of PCer in a similar manner as palmitoyl lyso-PC. When examined in the DOPC bilayer, it appeared that the association between palmitoyl lyso-PC and PCer was equimolar in nature. It is proposed that the interaction of PCer with lyso-PLs was driven by the need of ceramide to obtain a large-headgroup co-lipid, and saturated lyso-PLs were preferred co-lipids over DOPC because of the nature of their acyl chain. Structural analogs of PCer (1- or 3-deoxy-PCer) were also associated with palmitoyl lyso-PC, similarly to PCer, suggesting that the ceramide/lyso-PL interaction was not sensitive to structural alterations in the ceramide molecule. Binary complexes containing palmitoyl lyso-PC and ceramide were prepared, and these had a bilayer structure as ascertained by transmission electron microscopy. It is concluded that ceramides and lyso-PLs associated with each other both in binary bilayers and in ternary systems based on the DOPC bilayers. This association may have biological relevance under conditions in which both sphingomyelinases and phospholipase A2 enzymes are activated, such as during inflammatory processes.

Dataset Information

A Permeability Study of O2 and the Trace Amine p-Tyramine through Model Phosphatidylcholine Bilayers.

Publications

A Permeability Study of O2 and the Trace Amine p-Tyramine through Model Phosphatidylcholine Bilayers.

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