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Current understanding of the mechanisms by which membrane-active peptides permeate and disrupt model lipid membranes

Sun, Delin; Forsman, Jan LU and Woodward, Clifford E. (2016) In Current Topics in Medicinal Chemistry 16(2). p.170-186
Abstract

Three classes of membrane active peptides (MAPs) are considered in this review: cell penetrating peptides (CPPs); anti-microbial peptides (AMPs), and amyloidal peptides. We summarize both experimental and theoretical results for several representative peptides in these different classes, which highlight commonalities in their interactions with model lipid membranes. While it is clear that no fixed set of mechanisms completely characterize any particular class of MAPs, there is certainly evidence that common mechanisms can be found within and between classes. For example, CPPs appear to undergo rapid translocation across lipid bilayers through small transient pores, which nevertheless appear not to cause persistent damage to membranes.... (More)

Three classes of membrane active peptides (MAPs) are considered in this review: cell penetrating peptides (CPPs); anti-microbial peptides (AMPs), and amyloidal peptides. We summarize both experimental and theoretical results for several representative peptides in these different classes, which highlight commonalities in their interactions with model lipid membranes. While it is clear that no fixed set of mechanisms completely characterize any particular class of MAPs, there is certainly evidence that common mechanisms can be found within and between classes. For example, CPPs appear to undergo rapid translocation across lipid bilayers through small transient pores, which nevertheless appear not to cause persistent damage to membranes. On the other hand, AMPs also show evidence of rapid translocation, but associated with this, is membrane rupture to form large pores, which are subsequently stabilized by peptide adsorption to the pore edges. This disruption to the membrane is presumably responsible for cell death. Amyloidal peptides also show evidence of stable large pore formation, however, the mechanism for pore stabilization appears linked with their ability to form fibrils and prefibrillar aggregates and oligomers. There is some evidence that pores and membrane defects in fact act as nucleation sites for these structures. Where possible we have related the experimental and theoretical work to our own simulation findings in an effort to produce a comprehensive, albeit speculative picture for the mechanisms of action for this important group of peptides.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amyloid peptides, Anti-microbial peptides, Cell-penetrating peptides, Lipid membrane, Membrane active peptides, Pore-formation
in
Current Topics in Medicinal Chemistry
volume
16
issue
2
pages
17 pages
publisher
Bentham Science Publishers
external identifiers
  • scopus:84974625362
ISSN
1568-0266
DOI
10.2174/1568026615666150812121241
language
English
LU publication?
yes
id
f31c0332-16d3-4ffb-9b62-bd0f5ecb8f8e
date added to LUP
2016-10-17 10:05:47
date last changed
2017-07-05 17:26:04
@article{f31c0332-16d3-4ffb-9b62-bd0f5ecb8f8e,
  abstract     = {<p>Three classes of membrane active peptides (MAPs) are considered in this review: cell penetrating peptides (CPPs); anti-microbial peptides (AMPs), and amyloidal peptides. We summarize both experimental and theoretical results for several representative peptides in these different classes, which highlight commonalities in their interactions with model lipid membranes. While it is clear that no fixed set of mechanisms completely characterize any particular class of MAPs, there is certainly evidence that common mechanisms can be found within and between classes. For example, CPPs appear to undergo rapid translocation across lipid bilayers through small transient pores, which nevertheless appear not to cause persistent damage to membranes. On the other hand, AMPs also show evidence of rapid translocation, but associated with this, is membrane rupture to form large pores, which are subsequently stabilized by peptide adsorption to the pore edges. This disruption to the membrane is presumably responsible for cell death. Amyloidal peptides also show evidence of stable large pore formation, however, the mechanism for pore stabilization appears linked with their ability to form fibrils and prefibrillar aggregates and oligomers. There is some evidence that pores and membrane defects in fact act as nucleation sites for these structures. Where possible we have related the experimental and theoretical work to our own simulation findings in an effort to produce a comprehensive, albeit speculative picture for the mechanisms of action for this important group of peptides.</p>},
  author       = {Sun, Delin and Forsman, Jan and Woodward, Clifford E.},
  issn         = {1568-0266},
  keyword      = {Amyloid peptides,Anti-microbial peptides,Cell-penetrating peptides,Lipid membrane,Membrane active peptides,Pore-formation},
  language     = {eng},
  month        = {10},
  number       = {2},
  pages        = {170--186},
  publisher    = {Bentham Science Publishers},
  series       = {Current Topics in Medicinal Chemistry},
  title        = {Current understanding of the mechanisms by which membrane-active peptides permeate and disrupt model lipid membranes},
  url          = {http://dx.doi.org/10.2174/1568026615666150812121241},
  volume       = {16},
  year         = {2016},
}