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Applied Microbiology and Biotechnology

, Volume 102, Issue 9, pp 3879–3892 | Cite as

Elementary processes for the entry of cell-penetrating peptides into lipid bilayer vesicles and bacterial cells

  • Md. Zahidul Islam
  • Sabrina Sharmin
  • Md. Moniruzzaman
  • Masahito Yamazaki
Mini-Review

Abstract

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.

Keywords

CPPs Transportan 10 Oligoarginine Large unilamellar vesicle Giant unilamellar vesicle Pore Prepore Leakage Bacterial cells 

Notes

Funding

This work was supported in part by a Grant-in-Aid for Scientific Research (B) (No. 15H04361) from the Japan Society for the Promotion of Science (JSPS) to M.Y. This work was also supported in part by the Cooperative Research Project of the Research Center for Biomedical Engineering.

Compliance with ethical standards

Ethical approval

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.

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Authors and Affiliations

  1. 1.Department of Biotechnology and Genetic EngineeringJahangirnagar UniversityDhakaBangladesh
  2. 2.Integrated Bioscience Section, Graduate School of Science and TechnologyShizuoka UniversityShizuokaJapan
  3. 3.Nanomaterials Research Division, Research Institute of ElectronicsShizuoka UniversityShizuokaJapan
  4. 4.Department of Physics, Graduate School of ScienceShizuoka UniversityShizuokaJapan

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