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Spontaneous Vesiculation and pH-Induced Disassembly of a Lysosomotropic Detergent: Impacts on Lysosomotropism and Lysosomal Delivery
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
Royal Institute Technology, Sweden.
University of Calif Davis, CA 95616 USA; University of Calif Davis, CA 95616 USA.
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2016 (English)In: LANGMUIR, ISSN 0743-7463, Vol. 32, no 50, 13566-13575 p.Article in journal (Refereed) Published
Abstract [en]

Lysosomotropic detergents (LDs) selectively rupture lysosomal membranes through mechanisms that have yet to be characterized. A consensus view, currently, holds that LDs, which are weakly basic, diffuse across cellular membranes as monomers in an uncharged state, and via protonation in the acidic lysosomal compartment, they become trapped, accumulate, and subsequently solubilize the membrane and induce lysosomal membrane permeabilization. Here we demonstrate that the lysosomotropic detergent O-methyl-serine dodecylamide hydrochloride (MSDH) spontaneously assembles into vesicles at, and above, cytosolic pH, and that the vesicles disassemble as the pH reaches 6.4 or lower. The aggregation commences at concentrations below the range of those used in cell studies. Assembly and disassembly of the vesicles was studied via dynamic light scattering, zeta potential measurements, cryo-TEM, and fluorescence correlation spectroscopy and was found to be reversible via control of the pH. Aggregation of MSDH into closed vesicles under cytosolic conditions is at variance with the commonly held view of LD behavior, and we propose that endocytotic pathways should be considered as possible routes of LD entry into lysosomes. We further demonstrate that MSDH vesicles can be loaded with fluorophores via a solution transition from low to high pH, for subsequent release when the pH is lowered again. The ability to encapsulate molecular cargo into MSDH vesicles together with its ability to disaggregate at low pH and to permeabilize the lysosomal membrane presents an intriguing possibility to use MSDH as a delivery system.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC , 2016. Vol. 32, no 50, 13566-13575 p.
National Category
Biophysics
Identifiers
URN: urn:nbn:se:liu:diva-134081DOI: 10.1021/acs.langmuir.6b03458ISI: 000390619900030PubMedID: 27936755OAI: oai:DiVA.org:liu-134081DiVA: diva2:1068896
Note

Funding Agencies|Swedish Research Council [2013-3214]; Konung Gustaf V och Drottning Victorias Frimurarestiftelse; Stiftelseforvaltningen Region Ostergotland [LIO-570261]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009-00971]; Linkoping University

Available from: 2017-01-26 Created: 2017-01-22 Last updated: 2017-02-20

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