Nano Secondary Ion Mass Spectrometry Imaging of Dopamine Distribution Across Nanometer Vesicles
Journal article, 2017

We report an approach to spatially resolve the content across nanometer neuroendocrine vesicles in nerve-like cells by correlating super high-resolution mass spectrometry imaging, NanoSIMS, with transmission electron microscopy (TEM). Furthermore, intracellular electrochemical cytometry at nanotip electrodes is used to count the number of molecules in individual vesicles to compare to imaged amounts in vesicles. Correlation between the NanoSIMS and TEM provides nanometer resolution of the inner structure of these organelles. Moreover, correlation with electrochemical methods provides a means to quantify and relate vesicle neurotransmitter content and release, which is used to explain the slow transfer of dopamine between vesicular compartments. These nanoanalytical tools reveal that dopamine loading/unloading between vesicular compartments, dense core and halo solution, is a kinetically limited process. The combination of NanoSIMS and TEM has been used to show the distribution profile of newly synthesized dopamine across individual vesicles. Our findings suggest that the vesicle inner morphology might regulate the neurotransmitter release event during open and closed exocytosis from dense core vesicles with hours of equilibrium needed to move significant amounts of catecholamine from the protein dense core despite its nanometer size.

electrochemistry

NanoSIMS

nanoimaging

vesicle content

nanocompartments

Author

Jelena Lovric

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Analytical Chemistry

Johan Dunevall

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Analytical Chemistry

Anna Larsson

University of Gothenburg

Lin Ren

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Analytical Chemistry

Shalini Andersson

AstraZeneca AB

Anders Meibom

Ecole Polytechnique Federale De Lausanne

Per Malmberg

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Analytical Chemistry

Michael Kurczy

AstraZeneca AB

Andrew Ewing

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Analytical Chemistry

ACS Nano

1936-0851 (ISSN) 1936-086X (eISSN)

Vol. 11 4 3446-3455

Subject Categories

Chemical Sciences

DOI

10.1021/acsnano.6b07233

More information

Latest update

5/3/2018 1