Elementary processes for the entry of cell-penetrating peptides into lipid bilayer vesicles and bacterial cells
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Cell-penetrating peptides (CPPs) can translocate across the plasma membrane of living eukaryotic cells and enter the cytosol without significantly affecting cell viability. Consequently, CPPs have been used for the intracellular delivery of biological cargo such as proteins and oligonucleotides. However, the mechanisms underlying the translocation of CPPs across the plasma membrane remain unclear. In this mini-review, we summarize the experimental results regarding the entry of CPPs into lipid bilayer vesicles obtained using three methods: the large unilamellar vesicle (LUV) suspension method, the giant unilamellar vesicle (GUV) suspension method, and the single GUV method. The advantages and disadvantages of these methods are also discussed. Experimental results to date clearly indicate that CPPs can translocate across lipid bilayers and enter the vesicle lumen. Three models for the mechanisms and pathways by which CPPs translocate across lipid bilayers are described: (A) through pores induced by CPPs, (B) through transient prepores, and (C) via formation of inverted micelles. Both the pathway of translocation and the efficiency of entry of CPPs depend on the lipid composition of the bilayer and the type of CPP. We also describe the interaction of CPPs with bacterial cells. Some CPPs have strong antimicrobial activities. There are two modes of action of CPPs on bacterial cells: CPPs can induce damage to the plasma membrane and thus increase permeability, or CPPs enter the cytosol of bacterial cells without damaging the plasma membrane. The information currently available on the elementary processes by which CPPs enter lipid bilayer vesicles and bacterial cells is valuable for elucidating the mechanisms of entry of CPPs into the cytosol of various eukaryotic cells.
KeywordsCPPs Transportan 10 Oligoarginine Large unilamellar vesicle Giant unilamellar vesicle Pore Prepore Leakage Bacterial cells
Compliance with ethical standards
This article does not contain any studies with human participants or animals performed by any of the authors.
Conflict of interest
The authors declare that they have no conflict of interest.
- Hille B (1992) Ionic channels of excitable membranes, 2nd edn. Sinauer Association Inc., MassachusettsGoogle Scholar
- Kawamoto S, Takasu M, Miyakawa T, Morikawa R, Oda T, Futaki S, Nagao H (2011) Inverted micelles formation of cell-penetrating peptide studied by coarse-grained simulation: importance of attractive force between cell-penetrating peptides and lipid head group. J Chem Phys 134:095103CrossRefPubMedGoogle Scholar
- Lipowsky R, Sackmann E (eds) (1995) Structure and dynamics of membranes. Elsevier Science BV, AmsterdamGoogle Scholar
- Mishra A, Lai GH, Schmidt NW, Sun VZ, Rodriguez AR, Tong R, Tang L, Cheng J, Deming TJ, Kamei DT, Wong GCL (2011) Translocation of HIV TAT peptide and analogues induced by multiplexed membrane and cytoskeletal interactions. Proc Natl Acad Sci U S A 108:16883–16888CrossRefPubMedPubMedCentralGoogle Scholar
- Seddon JM, Templer RH (1995) Polymorphism of lipid-water systems. In: Lipowsky R, Sackmann E (eds) Structure and dynamics of membranes. Elsevier Science BV, Amsterdam, pp 97–160Google Scholar
- Swiecicki J-M, Bartsch A, Tailhades J, Di Pisa M, Heller B, Chassaing G, Mansuy C, Burlina F, Lavielle S (2014) The efficacies of cell-penetrating peptides in accumulating in large unilamellar vesicles depend on their ability to form inverted micelles. Chembiochem 15:884–891CrossRefPubMedGoogle Scholar
- Wadia JS, Stan RV, Dowdy SE (2004) Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nat Med 37:147–195Google Scholar
- Yamazaki M, Miyazu M, Asano T, Yuba A, Kume N (1994) Direct evidence of induction of interdigitated gel structure in large unilamellar vesicles of dipalmitoylphophatidylcholine by ethanol: studies by excimer method and high-resolution electron cyromicroscopy. Biophys J 66:729–733CrossRefPubMedPubMedCentralGoogle Scholar