Advanced

Amphipathic Membrane-Active Peptides Recognize and Stabilize Ruptured Membrane Pores: Exploring Cause and Effect with Coarse-Grained Simulations

Sun, Delin; Forsman, Jan LU and Woodward, Clifford E. (2015) In Langmuir 31(2). p.752-761
Abstract
Induction of membrane pores has been suggested as the common molecular action by which a variety of amphipathic membrane-active peptides cause damage to cells. In this study, we have performed coarse-grained molecular dynamics simulations to establish two clear molecular processes that seem critical for the activity of amphipathic peptides. They are (i) the recognition and (ii) the stabilization of ruptured membrane pores. By considering 12 structurally different peptide types, we reveal that peptide secondary structure content, hydrophobicity, and length are important physicochemical factors that allow amphipathic peptides to aggregate in and stabilize ruptured membrane pores. The simulated inner diameters of peptide-stabilized membrane... (More)
Induction of membrane pores has been suggested as the common molecular action by which a variety of amphipathic membrane-active peptides cause damage to cells. In this study, we have performed coarse-grained molecular dynamics simulations to establish two clear molecular processes that seem critical for the activity of amphipathic peptides. They are (i) the recognition and (ii) the stabilization of ruptured membrane pores. By considering 12 structurally different peptide types, we reveal that peptide secondary structure content, hydrophobicity, and length are important physicochemical factors that allow amphipathic peptides to aggregate in and stabilize ruptured membrane pores. The simulated inner diameters of peptide-stabilized membrane pores are in good agreement with available experimental data. However, the orientations of a-helical peptides in the membrane pore were found to be quite dispersed. This supports recent challenges to the traditional depictions to peptide orientations in the classical toroidal and barrel-stave pore models. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Langmuir
volume
31
issue
2
pages
752 - 761
publisher
The American Chemical Society
external identifiers
  • wos:000348333700013
  • scopus:84922471062
ISSN
0743-7463
DOI
10.1021/la5038266
language
English
LU publication?
yes
id
acce0c9d-8e20-42d9-a9ca-be28413c4b13 (old id 5190631)
date added to LUP
2015-03-25 11:29:44
date last changed
2017-11-19 03:10:39
@article{acce0c9d-8e20-42d9-a9ca-be28413c4b13,
  abstract     = {Induction of membrane pores has been suggested as the common molecular action by which a variety of amphipathic membrane-active peptides cause damage to cells. In this study, we have performed coarse-grained molecular dynamics simulations to establish two clear molecular processes that seem critical for the activity of amphipathic peptides. They are (i) the recognition and (ii) the stabilization of ruptured membrane pores. By considering 12 structurally different peptide types, we reveal that peptide secondary structure content, hydrophobicity, and length are important physicochemical factors that allow amphipathic peptides to aggregate in and stabilize ruptured membrane pores. The simulated inner diameters of peptide-stabilized membrane pores are in good agreement with available experimental data. However, the orientations of a-helical peptides in the membrane pore were found to be quite dispersed. This supports recent challenges to the traditional depictions to peptide orientations in the classical toroidal and barrel-stave pore models.},
  author       = {Sun, Delin and Forsman, Jan and Woodward, Clifford E.},
  issn         = {0743-7463},
  language     = {eng},
  number       = {2},
  pages        = {752--761},
  publisher    = {The American Chemical Society},
  series       = {Langmuir},
  title        = {Amphipathic Membrane-Active Peptides Recognize and Stabilize Ruptured Membrane Pores: Exploring Cause and Effect with Coarse-Grained Simulations},
  url          = {http://dx.doi.org/10.1021/la5038266},
  volume       = {31},
  year         = {2015},
}