Contrasting roles for actin in the cellular uptake of cell penetrating peptide conjugates

Abstract The increased need for macromolecular therapeutics, such as peptides, proteins and nucleotides, to reach intracellular targets necessitates more effective delivery vectors and a higher level of understanding of their mechanism of action. Cell penetrating peptides (CPPs) can transport a rang...

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Autores principales:	L. He, E. J. Sayers, P. Watson, A. T. Jones
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/011dbd8a87fc44508d6fc52bf80a74a3
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spelling	oai:doaj.org-article:011dbd8a87fc44508d6fc52bf80a74a32021-12-02T16:07:51ZContrasting roles for actin in the cellular uptake of cell penetrating peptide conjugates10.1038/s41598-018-25600-82045-2322https://doaj.org/article/011dbd8a87fc44508d6fc52bf80a74a32018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25600-8https://doaj.org/toc/2045-2322Abstract The increased need for macromolecular therapeutics, such as peptides, proteins and nucleotides, to reach intracellular targets necessitates more effective delivery vectors and a higher level of understanding of their mechanism of action. Cell penetrating peptides (CPPs) can transport a range of macromolecules into cells, either through direct plasma membrane translocation or endocytosis. All known endocytic pathways involve cell-cortex remodelling, a process shown to be regulated by reorganisation of the actin cytoskeleton. Here using flow cytometry, confocal microscopy and a variety of actin inhibitors we identify how actin disorganisation in different cell types differentially influences the cellular entry of three probes: the CPP octaarginine – Alexa488 conjugate (R8-Alexa488), octaarginine conjugated Enhanced Green Fluorescent Protein (EGFP-R8), and the fluid phase probe dextran. Disrupting actin organisation in A431 skin epithelial cells dramatically increases the uptake of EGFP-R8 and dextran, and contrasts strongly to inhibitory effects observed with transferrin and R8 attached to the fluorophore Alexa488. This demonstrates that uptake of the same CPP can occur via different endocytic processes depending on the conjugated fluorescent entity. Overall this study highlights how cargo influences cell uptake of this peptide and that the actin cytoskeleton may act as a gateway or barrier to endocytosis of drug delivery vectors.L. HeE. J. SayersP. WatsonA. T. JonesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q L. He E. J. Sayers P. Watson A. T. Jones Contrasting roles for actin in the cellular uptake of cell penetrating peptide conjugates
description	Abstract The increased need for macromolecular therapeutics, such as peptides, proteins and nucleotides, to reach intracellular targets necessitates more effective delivery vectors and a higher level of understanding of their mechanism of action. Cell penetrating peptides (CPPs) can transport a range of macromolecules into cells, either through direct plasma membrane translocation or endocytosis. All known endocytic pathways involve cell-cortex remodelling, a process shown to be regulated by reorganisation of the actin cytoskeleton. Here using flow cytometry, confocal microscopy and a variety of actin inhibitors we identify how actin disorganisation in different cell types differentially influences the cellular entry of three probes: the CPP octaarginine – Alexa488 conjugate (R8-Alexa488), octaarginine conjugated Enhanced Green Fluorescent Protein (EGFP-R8), and the fluid phase probe dextran. Disrupting actin organisation in A431 skin epithelial cells dramatically increases the uptake of EGFP-R8 and dextran, and contrasts strongly to inhibitory effects observed with transferrin and R8 attached to the fluorophore Alexa488. This demonstrates that uptake of the same CPP can occur via different endocytic processes depending on the conjugated fluorescent entity. Overall this study highlights how cargo influences cell uptake of this peptide and that the actin cytoskeleton may act as a gateway or barrier to endocytosis of drug delivery vectors.
format	article
author	L. He E. J. Sayers P. Watson A. T. Jones
author_facet	L. He E. J. Sayers P. Watson A. T. Jones
author_sort	L. He
title	Contrasting roles for actin in the cellular uptake of cell penetrating peptide conjugates
title_short	Contrasting roles for actin in the cellular uptake of cell penetrating peptide conjugates
title_full	Contrasting roles for actin in the cellular uptake of cell penetrating peptide conjugates
title_fullStr	Contrasting roles for actin in the cellular uptake of cell penetrating peptide conjugates
title_full_unstemmed	Contrasting roles for actin in the cellular uptake of cell penetrating peptide conjugates
title_sort	contrasting roles for actin in the cellular uptake of cell penetrating peptide conjugates
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/011dbd8a87fc44508d6fc52bf80a74a3
work_keys_str_mv	AT lhe contrastingrolesforactininthecellularuptakeofcellpenetratingpeptideconjugates AT ejsayers contrastingrolesforactininthecellularuptakeofcellpenetratingpeptideconjugates AT pwatson contrastingrolesforactininthecellularuptakeofcellpenetratingpeptideconjugates AT atjones contrastingrolesforactininthecellularuptakeofcellpenetratingpeptideconjugates
_version_	1718384696193187840

Contrasting roles for actin in the cellular uptake of cell penetrating peptide conjugates

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