Direct entry of cell-penetrating peptide can be controlled by maneuvering the membrane curvature

Abstract A biomembrane's role is to be a barrier for interior cytosol from an exterior environment to execute the cell's normal biological functions. However, a water-soluble peptide called cell-penetrating peptide (CPP) has been known for its ability to directly penetrate through the biom...

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Autores principales:	Kazutami Sakamoto, Taku Morishita, Kenichi Aburai, Daisuke Ito, Tomohiro Imura, Kenichi Sakai, Masahiko Abe, Ikuhiko Nakase, Shiroh Futaki, Hideki Sakai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/016b653fec8c47258330dc698d6366b3
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spelling	oai:doaj.org-article:016b653fec8c47258330dc698d6366b32021-12-02T11:46:07ZDirect entry of cell-penetrating peptide can be controlled by maneuvering the membrane curvature10.1038/s41598-020-79518-12045-2322https://doaj.org/article/016b653fec8c47258330dc698d6366b32021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79518-1https://doaj.org/toc/2045-2322Abstract A biomembrane's role is to be a barrier for interior cytosol from an exterior environment to execute the cell's normal biological functions. However, a water-soluble peptide called cell-penetrating peptide (CPP) has been known for its ability to directly penetrate through the biomembranes into cells (cytolysis) without perturbating cell viability and expected to be a promising drug delivery vector. Examples of CPP include peptides with multiple arginine units with strong cationic properties, which is the key to cytolysis. Here we show the conclusive evidence to support the mechanism of CPP’s cytolysis and way to control it. The mechanism we proposed is attributed to biomembrane’s physicochemical nature as lamellar liquid crystal (Lα). Cytolysis occurs as the temporal and local dynamic phase transitions from Lα to an undulated lamellar with pores called Mesh1. We have shown this phase transfer of Lα composed of dioleoyl-phosphatidylcholine (DOPC) with water by adding oligo-arginine (Rx) as CPP at the equilibrium. Using giant unilamellar vesicle composed of DOPC as a single cell model, we could control the level of cytolysis of CPP (FITC-R8) by changing the curvature of the membrane through osmotic pressure modulation. The cytolysis of CPP utilizes biomembrane's inherent topological and functional flexibility corresponding to the stimuli.Kazutami SakamotoTaku MorishitaKenichi AburaiDaisuke ItoTomohiro ImuraKenichi SakaiMasahiko AbeIkuhiko NakaseShiroh FutakiHideki SakaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kazutami Sakamoto Taku Morishita Kenichi Aburai Daisuke Ito Tomohiro Imura Kenichi Sakai Masahiko Abe Ikuhiko Nakase Shiroh Futaki Hideki Sakai Direct entry of cell-penetrating peptide can be controlled by maneuvering the membrane curvature
description	Abstract A biomembrane's role is to be a barrier for interior cytosol from an exterior environment to execute the cell's normal biological functions. However, a water-soluble peptide called cell-penetrating peptide (CPP) has been known for its ability to directly penetrate through the biomembranes into cells (cytolysis) without perturbating cell viability and expected to be a promising drug delivery vector. Examples of CPP include peptides with multiple arginine units with strong cationic properties, which is the key to cytolysis. Here we show the conclusive evidence to support the mechanism of CPP’s cytolysis and way to control it. The mechanism we proposed is attributed to biomembrane’s physicochemical nature as lamellar liquid crystal (Lα). Cytolysis occurs as the temporal and local dynamic phase transitions from Lα to an undulated lamellar with pores called Mesh1. We have shown this phase transfer of Lα composed of dioleoyl-phosphatidylcholine (DOPC) with water by adding oligo-arginine (Rx) as CPP at the equilibrium. Using giant unilamellar vesicle composed of DOPC as a single cell model, we could control the level of cytolysis of CPP (FITC-R8) by changing the curvature of the membrane through osmotic pressure modulation. The cytolysis of CPP utilizes biomembrane's inherent topological and functional flexibility corresponding to the stimuli.
format	article
author	Kazutami Sakamoto Taku Morishita Kenichi Aburai Daisuke Ito Tomohiro Imura Kenichi Sakai Masahiko Abe Ikuhiko Nakase Shiroh Futaki Hideki Sakai
author_facet	Kazutami Sakamoto Taku Morishita Kenichi Aburai Daisuke Ito Tomohiro Imura Kenichi Sakai Masahiko Abe Ikuhiko Nakase Shiroh Futaki Hideki Sakai
author_sort	Kazutami Sakamoto
title	Direct entry of cell-penetrating peptide can be controlled by maneuvering the membrane curvature
title_short	Direct entry of cell-penetrating peptide can be controlled by maneuvering the membrane curvature
title_full	Direct entry of cell-penetrating peptide can be controlled by maneuvering the membrane curvature
title_fullStr	Direct entry of cell-penetrating peptide can be controlled by maneuvering the membrane curvature
title_full_unstemmed	Direct entry of cell-penetrating peptide can be controlled by maneuvering the membrane curvature
title_sort	direct entry of cell-penetrating peptide can be controlled by maneuvering the membrane curvature
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/016b653fec8c47258330dc698d6366b3
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Direct entry of cell-penetrating peptide can be controlled by maneuvering the membrane curvature

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