Role of Membrane Lipids for the Activity of Pore Forming Peptides and Proteins

Fuertes, Gustavo; Giménez, Diana; Esteban-Martín, Santi; García‐Sáez, Ana J.; Sánchez, Orlando A.; Salgado, Jesús

doi:10.1007/978-1-4419-6327-7_4

Cited by 26 publications

(15 citation statements)

References 207 publications

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“…1A) possess a cationic, amphiphilic structure that allows them to target the negatively charged membranes of cancer cells (and bacteria), but not normal mammalian cells (see below), and may have pore-forming activity. These peptides, which have an affinity for anionic phospholipid head groups, exert their cytotoxic effects by docking in target membranes and causing depolarization [3,4]. The mechanism of action underlying depolarization, in turn, is related to the ability of cationic, membrane-active peptides to form toroidal pores [3, 4].…”

Section: Introductionmentioning

confidence: 99%

“…These peptides, which have an affinity for anionic phospholipid head groups, exert their cytotoxic effects by docking in target membranes and causing depolarization [3,4]. The mechanism of action underlying depolarization, in turn, is related to the ability of cationic, membrane-active peptides to form toroidal pores [3, 4]. In a toroidal pore, as compared to a “barrel stave” pore, the peptides and lipids assemble into a type of organized, supra-molecular structure, causing curvature of the membrane to form a pore through which ions or small molecules can pass (Fig.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Use of Therapeutic Peptides to Target and to Kill Cancer Cells

Boohaker¹,

Lee²,

Vishnubhotla³

et al. 2012

CMC

293

219

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Peptide therapeutics is a promising field for emerging anti-cancer agents. Benefits include the ease and rapid synthesis of peptides and capacity for modifications. An existing and vast knowledge base of protein structure and function can be exploited for novel peptide design. Current research focuses on developing peptides that can (1) serve as tumor targeting moieties and (2) permeabilize membranes with cytotoxic consequences. A survey of recent findings reveals significant trends. Amphiphilic peptides with clusters of hydrophobic and cationic residues are features of anti-microbial peptides that confer the ability to eradicate microbes and show considerable anti-cancer toxicity. Peptides that assemble and form pores can disrupt cell or organelle membranes and cause apoptotic or necrotic death. Cell permeable and tumor-homing peptides can carry biologically active cargo to tumors or tumor vasculature. The challenge lies in developing the clinical application of therapeutic peptides. Improving delivery to tumors, minimizing non-specific toxic effects and discerning pharmacokinetic properties are high among the needs to produce a powerful therapeutic peptide for cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Use of Therapeutic Peptides to Target and to Kill Cancer Cells

Boohaker¹,

Lee²,

Vishnubhotla³

et al. 2012

CMC

293

219

View full text Add to dashboard Cite

show abstract

“…An alternative view, however, regards biological membranes as dynamic supramolecular complexes, where lipids are active components even in functions usually assigned to proteins (Fuertes et al. 2010b). The lipids impose specific physical properties on the bilayer, determining its degree of order, fluidity, and thickness, and in some cases being responsible for the formation of domains (Simons and Vaz 2004).…”

Section: Introductionmentioning

confidence: 99%

A lipocentric view of peptide-induced pores

et al. 2011

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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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“…Profilin interaction with phosphatidylinositol (4,5)bisphosphate (Krishnan et al 2009), caspase-8/Bid-FL complex binding to cardiolipin (Jalmar et al 2010), tBID interaction with BCL(XL) (Garcia-Saez et al 2009), and the activity of pore forming peptides (Fuertes et al 2010) are some of the biological processes where GUVs have been used as model platforms. The distribution and the mobility of the lipid-anchored oligopeptide-binding protein OppA, the translocator complex OppBCDF of the oligopeptide ABC transporter, the mechanosensitive channel of MscL and the secondary lactose transport protein LacS were studied using GUVs (Doeven et al 2005).…”

Section: Giant Unilamellar Vesicles (Guvs)mentioning

confidence: 99%

Model membrane platforms to study protein-membrane interactions

Sezgin

Schwille

2012

Molecular Membrane Biology

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Constituting functional interactions between proteins and lipid membranes is one of the essential features of cellular membranes. The major challenge of quantitatively studying these interactions in living cells is the multitude of involved components that are difficult, if not impossible, to simultaneously control. Therefore, there is great need for simplified but still sufficiently detailed model systems to investigate the key constituents of biological processes. To specifically focus on interactions between membrane proteins and lipids, several membrane models have been introduced which recapitulate to varying degrees the complexity and physicochemical nature of biological membranes. Here, we summarize the presently most widely used minimal model membrane systems, namely Supported Lipid Bilayers (SLBs), Giant Unilamellar Vesicles (GUVs) and Giant Plasma Membrane Vesicles (GPMVs) and their applications for protein-membrane interactions.

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Role of Membrane Lipids for the Activity of Pore Forming Peptides and Proteins

Cited by 26 publications

References 207 publications

The Use of Therapeutic Peptides to Target and to Kill Cancer Cells

The Use of Therapeutic Peptides to Target and to Kill Cancer Cells

A lipocentric view of peptide-induced pores

Model membrane platforms to study protein-membrane interactions

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