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Effect of Vesicle Size on the Cytolysis of Cell-Penetrating Peptides (CPPs)

Authors :
Kazutami Sakamoto
Takeshi Kitano
Haruka Kuwahara
Megumi Tedani
Kenichi Aburai
Shiroh Futaki
Masahiko Abe
Hideki Sakai
Hiroyasu Ohtaka
Yuji Yamashita
Source :
International Journal of Molecular Sciences, Vol 21, Iss 19, p 7405 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

A specific series of peptides, called a cell-penetrating peptide (CPP), is known to be free to directly permeate through cell membranes into the cytosol (cytolysis); hence, this CPP would be a potent carrier for a drug delivery system (DDS). Previously, we proposed the mechanism of cytolysis as a temporal and local phase transfer of membrane lipid caused by positive membrane curvature generation. Moreover, we showed how to control the CPP cytolysis. Here, we investigate the phospholipid vesicle’s size effect on CPP cytolysis because this is the most straightforward way to control membrane curvature. Contrary to our expectation, we found that the smaller the vesicle diameter (meaning a higher membrane curvature), the more cytolysis was suppressed. Such controversial findings led us to seek the reason for the unexpected results, and we ended up finding out that the mobility of membrane lipids as a liquid crystal is the key to cytolysis. As a result, we could explain the cause of cytolysis suppression by reducing the vesicle size (because of the restriction of lipid mobility); osmotic pressure reduction to enhance positive curvature generation works as long as the membrane is mobile enough to modulate the local structure. Taking all the revealed vital factors and their effects as a tool, we will further explore how to control CPP cytolysis for developing a DDS system combined with appropriate cargo selection to be tagged with CPPs.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
21
Issue :
19
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.248444136cdf4e51a38f7a5e9d3d4c01
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms21197405