Cargando…

Interactions of the Lysosomotropic Detergent O-Methyl-Serine Dodecylamide Hydrochloride (MSDH) with Lipid Bilayer Membranes—Implications for Cell Toxicity

O-methyl-serine dodecylamine hydrochloride (MSDH) is a detergent that accumulates selectively in lysosomes, a so-called lysosomotropic detergent, with unexpected chemical properties. At physiological pH, it spontaneously forms vesicles, which disassemble into small aggregates (probably micelles) bel...

Descripción completa

Detalles Bibliográficos
Autores principales: Villamil Giraldo, Ana-Maria, Eriksson, Ida, Wennmalm, Stefan, Fyrner, Timmy, Ederth, Thomas, Öllinger, Karin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247706/
https://www.ncbi.nlm.nih.gov/pubmed/32365555
http://dx.doi.org/10.3390/ijms21093136
_version_ 1783538215472332800
author Villamil Giraldo, Ana-Maria
Eriksson, Ida
Wennmalm, Stefan
Fyrner, Timmy
Ederth, Thomas
Öllinger, Karin
author_facet Villamil Giraldo, Ana-Maria
Eriksson, Ida
Wennmalm, Stefan
Fyrner, Timmy
Ederth, Thomas
Öllinger, Karin
author_sort Villamil Giraldo, Ana-Maria
collection PubMed
description O-methyl-serine dodecylamine hydrochloride (MSDH) is a detergent that accumulates selectively in lysosomes, a so-called lysosomotropic detergent, with unexpected chemical properties. At physiological pH, it spontaneously forms vesicles, which disassemble into small aggregates (probably micelles) below pH 6.4. In this study, we characterize the interaction between MSDH and liposomes at different pH and correlate the findings to toxicity in human fibroblasts. We find that the effect of MSDH on lipid membranes is highly pH-dependent. At neutral pH, the partitioning of MSDH into the liposome membrane is immediate and causes the leakage of small fluorophores, unless the ratio between MSDH and lipids is kept low. At pH 5, the partitioning of MSDH into the membrane is kinetically impeded since MSDH is charged and a high ratio between MSDH and the lipids is required to permeabilize the membrane. When transferred to cell culture conditions, the ratio between MSDH and plasma membrane lipids must therefore be low, at physiological pH, to maintain plasma membrane integrity. Transmission electron microscopy suggests that MSDH vesicles are taken up by endocytosis. As the pH of the endosomal compartment progressively drops, MSDH vesicles disassemble, leading to a high concentration of increasingly charged MSDH in small aggregates inside the lysosomes. At sufficiently high MSDH concentrations, the lysosome is permeabilized, the proteolytic content released to the cytosol and apoptotic cell death is induced.
format Online
Article
Text
id pubmed-7247706
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72477062020-06-10 Interactions of the Lysosomotropic Detergent O-Methyl-Serine Dodecylamide Hydrochloride (MSDH) with Lipid Bilayer Membranes—Implications for Cell Toxicity Villamil Giraldo, Ana-Maria Eriksson, Ida Wennmalm, Stefan Fyrner, Timmy Ederth, Thomas Öllinger, Karin Int J Mol Sci Article O-methyl-serine dodecylamine hydrochloride (MSDH) is a detergent that accumulates selectively in lysosomes, a so-called lysosomotropic detergent, with unexpected chemical properties. At physiological pH, it spontaneously forms vesicles, which disassemble into small aggregates (probably micelles) below pH 6.4. In this study, we characterize the interaction between MSDH and liposomes at different pH and correlate the findings to toxicity in human fibroblasts. We find that the effect of MSDH on lipid membranes is highly pH-dependent. At neutral pH, the partitioning of MSDH into the liposome membrane is immediate and causes the leakage of small fluorophores, unless the ratio between MSDH and lipids is kept low. At pH 5, the partitioning of MSDH into the membrane is kinetically impeded since MSDH is charged and a high ratio between MSDH and the lipids is required to permeabilize the membrane. When transferred to cell culture conditions, the ratio between MSDH and plasma membrane lipids must therefore be low, at physiological pH, to maintain plasma membrane integrity. Transmission electron microscopy suggests that MSDH vesicles are taken up by endocytosis. As the pH of the endosomal compartment progressively drops, MSDH vesicles disassemble, leading to a high concentration of increasingly charged MSDH in small aggregates inside the lysosomes. At sufficiently high MSDH concentrations, the lysosome is permeabilized, the proteolytic content released to the cytosol and apoptotic cell death is induced. MDPI 2020-04-29 /pmc/articles/PMC7247706/ /pubmed/32365555 http://dx.doi.org/10.3390/ijms21093136 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Villamil Giraldo, Ana-Maria
Eriksson, Ida
Wennmalm, Stefan
Fyrner, Timmy
Ederth, Thomas
Öllinger, Karin
Interactions of the Lysosomotropic Detergent O-Methyl-Serine Dodecylamide Hydrochloride (MSDH) with Lipid Bilayer Membranes—Implications for Cell Toxicity
title Interactions of the Lysosomotropic Detergent O-Methyl-Serine Dodecylamide Hydrochloride (MSDH) with Lipid Bilayer Membranes—Implications for Cell Toxicity
title_full Interactions of the Lysosomotropic Detergent O-Methyl-Serine Dodecylamide Hydrochloride (MSDH) with Lipid Bilayer Membranes—Implications for Cell Toxicity
title_fullStr Interactions of the Lysosomotropic Detergent O-Methyl-Serine Dodecylamide Hydrochloride (MSDH) with Lipid Bilayer Membranes—Implications for Cell Toxicity
title_full_unstemmed Interactions of the Lysosomotropic Detergent O-Methyl-Serine Dodecylamide Hydrochloride (MSDH) with Lipid Bilayer Membranes—Implications for Cell Toxicity
title_short Interactions of the Lysosomotropic Detergent O-Methyl-Serine Dodecylamide Hydrochloride (MSDH) with Lipid Bilayer Membranes—Implications for Cell Toxicity
title_sort interactions of the lysosomotropic detergent o-methyl-serine dodecylamide hydrochloride (msdh) with lipid bilayer membranes—implications for cell toxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247706/
https://www.ncbi.nlm.nih.gov/pubmed/32365555
http://dx.doi.org/10.3390/ijms21093136
work_keys_str_mv AT villamilgiraldoanamaria interactionsofthelysosomotropicdetergentomethylserinedodecylamidehydrochloridemsdhwithlipidbilayermembranesimplicationsforcelltoxicity
AT erikssonida interactionsofthelysosomotropicdetergentomethylserinedodecylamidehydrochloridemsdhwithlipidbilayermembranesimplicationsforcelltoxicity
AT wennmalmstefan interactionsofthelysosomotropicdetergentomethylserinedodecylamidehydrochloridemsdhwithlipidbilayermembranesimplicationsforcelltoxicity
AT fyrnertimmy interactionsofthelysosomotropicdetergentomethylserinedodecylamidehydrochloridemsdhwithlipidbilayermembranesimplicationsforcelltoxicity
AT ederththomas interactionsofthelysosomotropicdetergentomethylserinedodecylamidehydrochloridemsdhwithlipidbilayermembranesimplicationsforcelltoxicity
AT ollingerkarin interactionsofthelysosomotropicdetergentomethylserinedodecylamidehydrochloridemsdhwithlipidbilayermembranesimplicationsforcelltoxicity