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Interactions of the...
Interactions of the lysosomotropic detergent omethyl-serine dodecylamide hydrochloride (Msdh) with lipid bilayer membranes-implications for cell toxicity
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- Villamil Giraldo, Ana-Maria, 1973- (författare)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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- Eriksson, Ida, 1985- (författare)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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- Wennmalm, Stefan, 1970- (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Biofysik,Royal Institute of Technology, Department of Applied Physics, Biophysics, Sweden
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- Fyrner, Timmy (författare)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Ederth, Thomas (författare)
- Linköpings universitet,Biofysik och bioteknik,Tekniska fakulteten
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- Öllinger, Karin, 1962- (författare)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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(creator_code:org_t)
- 2020-04-29
- 2020
- Engelska.
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:9
- Relaterad länk:
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https://doi.org/10.3...
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https://www.mdpi.com...
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https://liu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
- NATURVETENSKAP -- Kemi -- Fysikalisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Physical Chemistry (hsv//eng)
Nyckelord
- Liposome
- Lysosomal membrane permeabilization
- Lysosome
- Lysosomotropic detergent
- MSDH
- caspase 3
- detergent
- lactate dehydrogenase
- methyl serine dodecylamide hydrochloride
- n acetyl beta glucosaminidase
- unclassified drug
- AG1518 cell line
- apoptosis
- Article
- cell damage
- cell permeabilization
- cell viability
- confocal laser scanning microscopy
- controlled study
- cytotoxicity
- cytotoxicity assay
- endocytosis
- enzyme activity
- fibroblast cell line
- fluorescence correlation spectroscopy
- human
- human cell
- immunocytochemistry
- incubation time
- lipid bilayer
- live cell imaging
- molecular interaction
- molecular stability
- MTT assay
- pH
- photon correlation spectroscopy
- spectrofluorometry
- transmission electron microscopy
- Western blotting
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- art (ämneskategori)
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