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

Holland BW, Berry MD, Gray CG, Tomberli B - PLoS ONE (2015)

Bottom Line: The tyramine results are compared to previous experimental work at 298K.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).This agrees with older experimental results, in contrast to more recent work that has suggested there is a strong ambiguity in the pKa values.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada; Department of Physics, University of Guelph, Guelph, Ontario, Canada.

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.

No MeSH data available.


Related in: MedlinePlus

The position dependent diffusion coefficient, D(z), of tyr (NH2/OH) and tyr+ () across a POPC bilayer with the bilayer center at z = 0.The diffusion for tyr+ remains relatively constant once inside the bilayer. This is likely due to a water channel being created in the POPC through a strong interaction of water with the  group. The water follows tyr+ through and reduces its mobility while keeping it in a consistent environment. The tyr permeates without water and has mobility characteristics that correlate strongly with the bilayer density, including a densely packed region near the head groups and an area of high free volume at the center of the bilayer where the hydrocarbon tails meet.
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pone.0122468.g007: The position dependent diffusion coefficient, D(z), of tyr (NH2/OH) and tyr+ () across a POPC bilayer with the bilayer center at z = 0.The diffusion for tyr+ remains relatively constant once inside the bilayer. This is likely due to a water channel being created in the POPC through a strong interaction of water with the group. The water follows tyr+ through and reduces its mobility while keeping it in a consistent environment. The tyr permeates without water and has mobility characteristics that correlate strongly with the bilayer density, including a densely packed region near the head groups and an area of high free volume at the center of the bilayer where the hydrocarbon tails meet.

Mentions: The bulk diffusion values, D(∞), of tyr+ (∼ 0.65 × 10−5 cm2/s) and tyr (∼ 0.9–1 × 10−5 cm2/s) shown in Fig 7 are about 4–5 times lower than that of O2, consistent with the increase in molecular volume. There is a measurable difference between the D(∞) values, however, that cannot be explained by their near identical size and shape. The difference in bulk diffusion can be attributed to the dielectric friction experienced by ions as they travel through a polar medium [67]; the dielectric friction manifests itself as the extra dissipative work done by reorienting the solvent molecules’ dipoles as the charge moves through the medium. This long range phenomenon is also present within the bilayer, as D(z) for tyr+ stays at a near constant value below that of tyr until well past the hydrophobic interface. Both D(z) values decrease at nearly the same rate while entering the headgroup region of the bilayer, but begin to diverge as they enter the hydrophobic acyl chain region. The unprotonated species shows an increase in diffusivity toward the center of the bilayer similar to that of O2 and water [28], while the tyr+ value stays at ∼ 0.2 × 10−5 cm2/s. This is probably due to the hydration shell that accompanies tyr+, keeping it in a more consistent environment throughout the hydrocarbon region. The increase in diffusion experienced by the unaccompanied tyr is likely due—as with O2 and water—to the greater availability of free volume toward the bilayer center [68].


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

Holland BW, Berry MD, Gray CG, Tomberli B - PLoS ONE (2015)

The position dependent diffusion coefficient, D(z), of tyr (NH2/OH) and tyr+ () across a POPC bilayer with the bilayer center at z = 0.The diffusion for tyr+ remains relatively constant once inside the bilayer. This is likely due to a water channel being created in the POPC through a strong interaction of water with the  group. The water follows tyr+ through and reduces its mobility while keeping it in a consistent environment. The tyr permeates without water and has mobility characteristics that correlate strongly with the bilayer density, including a densely packed region near the head groups and an area of high free volume at the center of the bilayer where the hydrocarbon tails meet.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4472697&req=5

pone.0122468.g007: The position dependent diffusion coefficient, D(z), of tyr (NH2/OH) and tyr+ () across a POPC bilayer with the bilayer center at z = 0.The diffusion for tyr+ remains relatively constant once inside the bilayer. This is likely due to a water channel being created in the POPC through a strong interaction of water with the group. The water follows tyr+ through and reduces its mobility while keeping it in a consistent environment. The tyr permeates without water and has mobility characteristics that correlate strongly with the bilayer density, including a densely packed region near the head groups and an area of high free volume at the center of the bilayer where the hydrocarbon tails meet.
Mentions: The bulk diffusion values, D(∞), of tyr+ (∼ 0.65 × 10−5 cm2/s) and tyr (∼ 0.9–1 × 10−5 cm2/s) shown in Fig 7 are about 4–5 times lower than that of O2, consistent with the increase in molecular volume. There is a measurable difference between the D(∞) values, however, that cannot be explained by their near identical size and shape. The difference in bulk diffusion can be attributed to the dielectric friction experienced by ions as they travel through a polar medium [67]; the dielectric friction manifests itself as the extra dissipative work done by reorienting the solvent molecules’ dipoles as the charge moves through the medium. This long range phenomenon is also present within the bilayer, as D(z) for tyr+ stays at a near constant value below that of tyr until well past the hydrophobic interface. Both D(z) values decrease at nearly the same rate while entering the headgroup region of the bilayer, but begin to diverge as they enter the hydrophobic acyl chain region. The unprotonated species shows an increase in diffusivity toward the center of the bilayer similar to that of O2 and water [28], while the tyr+ value stays at ∼ 0.2 × 10−5 cm2/s. This is probably due to the hydration shell that accompanies tyr+, keeping it in a more consistent environment throughout the hydrocarbon region. The increase in diffusion experienced by the unaccompanied tyr is likely due—as with O2 and water—to the greater availability of free volume toward the bilayer center [68].

Bottom Line: The tyramine results are compared to previous experimental work at 298K.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).This agrees with older experimental results, in contrast to more recent work that has suggested there is a strong ambiguity in the pKa values.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada; Department of Physics, University of Guelph, Guelph, Ontario, Canada.

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.

No MeSH data available.


Related in: MedlinePlus