A lipocentric view of peptide-induced pores |
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Authors: | Gustavo Fuertes Diana Giménez Santi Esteban-Martín Orlando L Sánchez-Muñoz Jesús Salgado |
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Institution: | 1.Instituto de Ciencia Molecular,Universitat de València,Paterna Valencia,Spain;2.Departamento de Bioquímica y Biología Molecular,Universitat de València,Burjassot Valencia,Spain;3.Institute for Research in Biomedicine,Barcelona,Spain |
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Abstract: | Although lipid membranes serve as effective sealing barriers for the passage of most polar solutes, nonmediated leakage is
not completely improbable. A high activation energy normally keeps unassisted bilayer permeation at a very low frequency,
but lipids are able to self-organize as pores even in peptide-free and protein-free membranes. The probability of leakage
phenomena increases under conditions such as phase coexistence, external stress or perturbation associated to binding of nonlipidic
molecules. Here, we argue that pore formation can be viewed as an intrinsic property of lipid bilayers, with strong similarities
in the structure and mechanism between pores formed with participation of peptides, lipidic pores induced by different types
of stress, and spontaneous transient bilayer defects driven by thermal fluctuations. Within such a lipocentric framework,
amphipathic peptides are best described as pore-inducing rather than pore-forming elements. Active peptides bound to membranes
can be understood as a source of internal surface tension which facilitates pore formation by diminishing the high activation
energy barrier. This first or immediate action of the peptide has some resemblance to catalysis. However, the presence of
membrane-active peptides has the additional effect of displacing the equilibrium towards the pore-open state, which is then
maintained over long times, and reducing the size of initial individual pores. Thus, pore-inducing peptides, regardless of
their sequence and oligomeric organization, can be assigned a double role of increasing the probability of pore formation
in membranes to high levels as well as stabilizing these pores after they appear. |
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