Development of lysosome-mimicking vesicles to study the effect of abnormal accumulation of sphingosine on membrane properties

Abstract Synthetic systems are widely used to unveil the molecular mechanisms of complex cellular events. Artificial membranes are key examples of models employed to address lipid-lipid and lipid-protein interactions. In this work, we developed a new synthetic system that more closely resembles the...

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Autores principales:	Ana C. Carreira, Rodrigo F. M. de Almeida, Liana C. Silva
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/554c648fab0940dcabdb3c56a3111c74
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spelling	oai:doaj.org-article:554c648fab0940dcabdb3c56a3111c742021-12-02T15:04:59ZDevelopment of lysosome-mimicking vesicles to study the effect of abnormal accumulation of sphingosine on membrane properties10.1038/s41598-017-04125-62045-2322https://doaj.org/article/554c648fab0940dcabdb3c56a3111c742017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04125-6https://doaj.org/toc/2045-2322Abstract Synthetic systems are widely used to unveil the molecular mechanisms of complex cellular events. Artificial membranes are key examples of models employed to address lipid-lipid and lipid-protein interactions. In this work, we developed a new synthetic system that more closely resembles the lysosome – the lysosome-mimicking vesicles (LMVs) – displaying stable acid-to-neutral pH gradient across the membrane. To evaluate the advantages of this synthetic system, we assessed the distinct effects of sphingosine (Sph) accumulation in membrane structure and biophysical properties of standard liposomes (no pH gradient) and in LMVs with lipid composition tuned to mimic physiological- or NPC1-like lysosomes. Ternary 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/Sphingomyelin (SM)/Cholesterol (Chol) mixtures with, respectively, low and high Chol/SM levels were prepared. The effect of Sph on membrane permeability and biophysical properties was evaluated by fluorescence spectroscopy, electrophoretic and dynamic light scattering. The results showed that overall Sph has the ability to cause a shift in vesicle surface charge, increase membrane order and promote a rapid increase in membrane permeability. These effects are enhanced in NPC1- LMVs. The results suggest that lysosomal accumulation of these lipids, as observed under pathological conditions, might significantly affect lysosomal membrane structure and integrity, and therefore contribute to the impairment of cell function.Ana C. CarreiraRodrigo F. M. de AlmeidaLiana C. SilvaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ana C. Carreira Rodrigo F. M. de Almeida Liana C. Silva Development of lysosome-mimicking vesicles to study the effect of abnormal accumulation of sphingosine on membrane properties
description	Abstract Synthetic systems are widely used to unveil the molecular mechanisms of complex cellular events. Artificial membranes are key examples of models employed to address lipid-lipid and lipid-protein interactions. In this work, we developed a new synthetic system that more closely resembles the lysosome – the lysosome-mimicking vesicles (LMVs) – displaying stable acid-to-neutral pH gradient across the membrane. To evaluate the advantages of this synthetic system, we assessed the distinct effects of sphingosine (Sph) accumulation in membrane structure and biophysical properties of standard liposomes (no pH gradient) and in LMVs with lipid composition tuned to mimic physiological- or NPC1-like lysosomes. Ternary 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/Sphingomyelin (SM)/Cholesterol (Chol) mixtures with, respectively, low and high Chol/SM levels were prepared. The effect of Sph on membrane permeability and biophysical properties was evaluated by fluorescence spectroscopy, electrophoretic and dynamic light scattering. The results showed that overall Sph has the ability to cause a shift in vesicle surface charge, increase membrane order and promote a rapid increase in membrane permeability. These effects are enhanced in NPC1- LMVs. The results suggest that lysosomal accumulation of these lipids, as observed under pathological conditions, might significantly affect lysosomal membrane structure and integrity, and therefore contribute to the impairment of cell function.
format	article
author	Ana C. Carreira Rodrigo F. M. de Almeida Liana C. Silva
author_facet	Ana C. Carreira Rodrigo F. M. de Almeida Liana C. Silva
author_sort	Ana C. Carreira
title	Development of lysosome-mimicking vesicles to study the effect of abnormal accumulation of sphingosine on membrane properties
title_short	Development of lysosome-mimicking vesicles to study the effect of abnormal accumulation of sphingosine on membrane properties
title_full	Development of lysosome-mimicking vesicles to study the effect of abnormal accumulation of sphingosine on membrane properties
title_fullStr	Development of lysosome-mimicking vesicles to study the effect of abnormal accumulation of sphingosine on membrane properties
title_full_unstemmed	Development of lysosome-mimicking vesicles to study the effect of abnormal accumulation of sphingosine on membrane properties
title_sort	development of lysosome-mimicking vesicles to study the effect of abnormal accumulation of sphingosine on membrane properties
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/554c648fab0940dcabdb3c56a3111c74
work_keys_str_mv	AT anaccarreira developmentoflysosomemimickingvesiclestostudytheeffectofabnormalaccumulationofsphingosineonmembraneproperties AT rodrigofmdealmeida developmentoflysosomemimickingvesiclestostudytheeffectofabnormalaccumulationofsphingosineonmembraneproperties AT lianacsilva developmentoflysosomemimickingvesiclestostudytheeffectofabnormalaccumulationofsphingosineonmembraneproperties
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Development of lysosome-mimicking vesicles to study the effect of abnormal accumulation of sphingosine on membrane properties

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