help button home button Biophys. J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Biophys. J. BioFAST: First Published January 13, 2006. doi:10.1529/biophysj.105.071977
© 2006 by the Biophysical Society.

A more recent version of this article appeared on April 1, 2006.
This Article
Right arrow Full Text (Rapid PDF)
Right arrow Supplemental
Right arrow All Versions of this Article:
biophysj.105.071977v1
90/7/2414    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Anishkin, A.
Right arrow Articles by Colombini, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Anishkin, A.
Right arrow Articles by Colombini, M.

MEMBRANES

Searching for the molecular arrangement of transmembrane ceramide channels

Andriy Anishkin 1*, Sergei Sukharev 1 and Marco Colombini 1

1 University of Maryland

* To whom correspondence should be addressed. E-mail: anisan{at}umd.edu.

Submitted on August 2, 2005
Revised on September 8, 2005
Accepted on 28 December 2005


  Abstract
Ceramides have been implicated in the initiation of apoptosis by permeabilizing the mitochondrial outer membrane to small proteins, including cytochrome c. In addition, ceramides were shown to form large metastable channels in planar membranes and liposomes (Siskind and Colombini, 2001) indicating that these lipids permeabilize membranes directly. Here we analyze molecular models of ceramide channels and test their stability in MD simulations. The structural units are columns of four to six ceramides H-bonded via amide groups and arranged as staves in either a parallel or anti-parallel manner. Two cylindrical assemblies of 14 columns (4 or 6 molecules per column) were embedded in a fully hydrated POPC phospholipid bilayer, and simulated for 24 ns in total. After equilibration, the water-filled pore adopted an hourglass-like shape as head groups of ceramides and phospholipids formed a smooth continuous interface. The structure-stabilizing interactions were both hydrogen bonds between the headgroups (including water- mediated interactions) and packing of the hydrocarbon tails. Ceramide's essential double bond reduced the mobility of the hydrocarbon tails and stabilized their packing. The 6-column assembly remained stable throughout a 10-ns simulation. During simulations of 4-column assemblies, pairs of columns displayed the tendency of splitting out from the channels, consistent with the previously proposed mechanism of channel disassembly.

Key Words: apoptosis, membrane, mitochondria, molecular dynamics, pore, sphingolipids




This article has been cited by other articles:


Home page
 Biophys. JHome page
R. Notman, W. K. den Otter, M. G. Noro, W. J. Briels, and J. Anwar
The Permeability Enhancing Mechanism of DMSO in Ceramide Bilayers Simulated by Molecular Dynamics
Biophys. J., September 15, 2007; 93(6): 2056 - 2068.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
M. J. Elrick, S. Fluss, and M. Colombini
Sphingosine, a Product of Ceramide Hydrolysis, Influences the Formation of Ceramide Channels
Biophys. J., September 1, 2006; 91(5): 1749 - 1756.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2006 by the Biophysical Society.