Unassisted Transport of N-acetyl-L-tryptophanamide through Membrane: Experiment and Simulation of Kinetics

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Issue Date
2012-03-08Author
Cardenas, Alfredo E.
Jas, Gouri S.
DeLeon, Kristine Y.
Hegefeld, Wendy A.
Kuczera, Krzysztof
Elber, Ron
Publisher
American Chemical Society
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Rights
This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of Physical Chemistry B, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jp2102447.
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Show full item recordAbstract
Cellular transport machinery, such as channels and pumps, is working against the background of unassisted material transport through membranes. The permeation of a blocked tryptophan through a 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) membrane is investigated to probe unassisted or physical transport. The transport rate is measured experimentally and modeled computationally. The time scale measured by Parallel Artificial Membrane Permeation Assay (PAMPA) experiments is ~8 h. Simulations with the Milestoning algorithm suggest Mean First Passage Time (MFPT) of ~4 h and the presence of a large barrier at the center of the bilayer. A similar calculation with the solubility-diffusion model yields MFPT of ~15 min. This permeation rate is nine orders of magnitude slower than the permeation rate of only a tryptophan side chain (computed by us and others). This difference suggests critical dependence of transport time on permeant size and hydrophilicity. Analysis of the simulation results suggests that the permeant partially preserves hydrogen bonding of the peptide backbone to water and lipid molecules even when it is moving closer to the bilayer center. As a consequence, defects of the membrane structure are developed to assist permeation.
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Citation
Cardenas, A. E., Jas, G. S., DeLeon, K. Y., Hegefeld, W. A., Kuczera, K., & Elber, R. (2012). Unassisted Transport of N-acetyl-L-tryptophanamide through Membrane: Experiment and Simulation of Kinetics. The Journal of Physical Chemistry. B, 116(9), 2739–2750. http://doi.org/10.1021/jp2102447
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