Title:Current Understanding of the Mechanisms by which Membrane-Active Peptides Permeate and Disrupt Model Lipid Membranes
VOLUME: 16 ISSUE: 2
Author(s):Delin Sun, Jan Forsman and Clifford E. Woodward
Affiliation:School of Physical, Environmental and Mathematical Sciences, University of New South Wales, Canberra ACT 2600, Australia.
Keywords:Amyloid peptides, Anti-microbial peptides, Cell-penetrating peptides, Lipid membrane, Membrane active peptides,
Pore-formation.
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. 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.
