The Cell Penetrating Peptides pVEC and W2-pVEC Induce Transformation of Gel Phase Domains in Phospholipid Bilayers without Affecting Their Integrity

Herbig, Michael E.; Assi, Fabiano; Textor, Marcus; Merkle, Hans P.

doi:10.1021/bi050923c

Cited by 37 publications

(28 citation statements)

References 61 publications

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“…Indeed, membrane penetration by synthetic 10 as well as by biologically derived 11 molecules/particles is currently under intense investigation. Some biomacromolecules, such as cell-penetrating peptides (CPPs), may be capable of penetrating membranes without overt lipid bilayer disruption/poration [12][13][14][15] . Likewise, synthetic nanomaterials with very small dimensions (molecules, metal nanoclusters 16 , small dendrimers 10 and carbon nanotubes 17 ) can also pass through cell membranes.…”

mentioning

confidence: 99%

“…Previous studies have shown that some cationic nanoparticles and macromolecules penetrate the plasma membrane of cells by generating transient holes 10 ; in contrast, some data suggest that a subset of biological membrane-penetrating macromolecules (for example, CPPs) may be capable of penetrating membranes without causing overt membrane poration [12][13][14][15] . The former mechanism can lead to cell death due to loss of membrane polarization and/or leakage of ions and molecules into/out of the cell.…”

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confidence: 99%

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Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles

Verma¹,

Uzun²,

et al. 2008

Nature Mater

1,182

1,203

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Nanoscale objects are typically internalized by cells into membrane-bounded endosomes and fail to access the cytosolic cell machinery. Whereas some biomacromolecules may penetrate or fuse with cell membranes without overt membrane disruption, no synthetic material of comparable size has shown this property yet. Cationic nano-objects pass through cell membranes by generating transient holes, a process associated with cytotoxicity. Studies aimed at generating cell-penetrating nanomaterials have focused on the effect of size, shape and composition. Here, we compare membrane penetration by two nanoparticle 'isomers' with similar composition (same hydrophobic content), one coated with subnanometre striations of alternating anionic and hydrophobic groups, and the other coated with the same moieties but in a random distribution. We show that the former particles penetrate the plasma membrane without bilayer disruption, whereas the latter are mostly trapped in endosomes. Our results offer a paradigm for analysing the fundamental problem of cell-membrane-penetrating bio-and macro-molecules. Nanomaterials are of great interest for use in biomedicine as imaging tools 1-3 , phototherapy agents 4,5 and gene delivery carriers 6,7 . Their interactions with cell membranes are of central importance for all such applications. For example, many drugdelivery systems are based on the transport of therapeutic agents to the cytosol or nucleus of cells by nanoparticles; efficient delivery must be achieved while avoiding cytotoxicity during passage through cell membranes to reach intracellular target compartments 8,9 . Indeed, membrane penetration by synthetic 10 as well as by biologically derived 11 molecules/particles is currently under intense investigation. Some biomacromolecules, such as cell-penetrating peptides (CPPs), may be capable of penetrating membranes without overt lipid bilayer disruption/poration 12-15 . Likewise, synthetic nanomaterials with very small dimensions (molecules, metal nanoclusters 16 , small dendrimers 10 and carbon nanotubes 17 ) can also pass through cell membranes. However, to the best of our knowledge, no synthetic material larger than a few nanometres in size can pass through membranes without disrupting the integrity of these biological barriers. For example, charged particles (such as cationic quantum dots or dendrimers, mostly assisted by some degree of hydrophobicity) induce transient poration of cell membranes to enter cells, a process associated with cytotoxicity 18 . Alternatively, nanoparticles have been designed to explicitly disrupt endolysosomal membranes to enter the cell by force 19 or enter the cell aided by exogenous agents such as CPP chaperones 20 . In contrast, most nanoparticles are trapped in endosomes 21 and hence do not reach the cytosol.The surface properties of nanomaterials play a critical role in determining the outcome of their interactions with cells 22 . Recently, we found that when gold nanoparticles are coated with binary mixtures of hydrophobic and hydrophilic organic mo...

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confidence: 99%

mentioning

confidence: 99%

Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles

Verma¹,

Uzun²,

et al. 2008

Nature Mater

1,182

1,203

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“…Cationic Au NPs with 50 per cent charge density (relative to hydrophobic ligands) effectively penetrated the lipid membrane without forming holes, whereas significant membrane disruption occurred at higher charge densities [46,57]. Certain cell-penetrating peptides are also known to translocate across membranes without lipid bilayer disruption [107][108][109]. The zwitterionic functionalization of the DPA-QDs used by Wang et al [44] may be responsible for the ability of these NPs to penetrate lipid membranes without compromising bilayer integrity.…”

Section: Passive Mechanisms Of Nanoparticle Uptake By Cellsmentioning

confidence: 99%

New views on cellular uptake and trafficking of manufactured nanoparticles

Treuel

Jiang

Nienhaus

2013

J. R. Soc. Interface.

306

224

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Nanoparticles (NPs) are of similar size to typical cellular components and proteins, and can efficiently intrude living cells. A detailed understanding of the involved processes at the molecular level is important for developing NPs designed for selective uptake by specific cells, for example, for targeted drug delivery. In addition, this knowledge can greatly assist in the engineering of NPs that should not penetrate cells so as to avoid adverse health effects. In recent years, a wide variety of experiments have been performed to elucidate the mechanisms underlying cellular NP uptake. Here, we review some select recent studies, which are often based on fluorescence microscopy and sophisticated strategies for specific labelling of key cellular components. We address the role of the protein corona forming around NPs in biological environments, and describe recent work revealing active endocytosis mechanisms and pathways involved in their cellular uptake. Passive uptake is also discussed. The current state of knowledge is summarized, and we point to issues that still need to be addressed to further advance our understanding of cellular NP uptake.

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“…Likewise, Matile and coworkers have shown that cationic peptides and hydrophobic anions can form neutral complexes that translocate across bilayers [30,31]. Merkle and coworkers have reported that the cationic peptide pVEC (and its derivatives) can induce phospholipid phase transitions, suggesting another mechanism by which PTDs could reach the cytosol [32].…”

Section: Why Is Polyarginine Internalized By Cells?mentioning

confidence: 99%

Internalization of cationic peptides: the road less (or more?) traveled

Fuchs

Raines

2006

Cell. Mol. Life Sci.

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Facilitating the entry of molecules into mammalian cells is of great interest to fields as diverse as cell biology and drug delivery. The discovery of natural protein transduction domains and the development of artificial ones, including polyarginine, provides a means to achieve this goal. Here, we comment on key chemical and biological aspects of cationic peptide internalization, including the physiological relevance of this process.

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The Cell Penetrating Peptides pVEC and W2-pVEC Induce Transformation of Gel Phase Domains in Phospholipid Bilayers without Affecting Their Integrity

Cited by 37 publications

References 61 publications

Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles

Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles

New views on cellular uptake and trafficking of manufactured nanoparticles

Internalization of cationic peptides: the road less (or more?) traveled

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