Microfluidics-based single cell analysis reveals drug-dependent motility changes in trypanosomes

Lab on a Chip
Axel HochstetterThomas Pfohl

Abstract

We present a single cell viability assay, based on chemical gradient microfluidics in combination with optical micromanipulation. Here, we used this combination to in situ monitor the effects of drugs and chemicals on the motility of the flagellated unicellular parasite Trypanosoma brucei; specifically, the local cell velocity and the mean squared displacement (MSD) of the cell trajectories. With our method, we are able to record in situ cell fixation by glutaraldehyde, and to quantify the critical concentration of 2-deoxy-d-glucose required to completely paralyze trypanosomes. In addition, we detected and quantified the impact on cell propulsion and energy generation at much lower 2-deoxy-d-glucose concentrations. Our microfluidics-based approach advances fast cell-based drug testing in a way that allows us to distinguish cytocidal from cytostatic drug effects, screen effective dosages, and investigate the impact on cell motility of drugs and chemicals. Using suramin, we could reveal the impact of the widely used drug on trypanosomes: suramin lowers trypanosome motility and induces cell-lysis after endocytosis.

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Citations

Jun 14, 2015·Trends in Parasitology·Víctor Seco-HidalgoLuis Miguel De Pablos
May 10, 2016·Trends in Parasitology·Axel Hochstetter, Thomas Pfohl
Oct 6, 2017·Pathogens·Michael P BarrettAxel Hochstetter
Dec 11, 2019·Bioengineering·Jack Merrin
Aug 19, 2018·Optics Express·Pontus NordenfeltAxel Hochstetter
Dec 26, 2018·Advanced Science·Jialang ZhuangYuanqing Zhang
Jun 22, 2018·High-throughput·Clément RegnaultAxel Hochstetter
Jan 3, 2021·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Chuan YangLiwu Fu
May 20, 2021·Journal of Travel Medicine·Perry J J van GenderenJaap J van Hellemond
Aug 28, 2020·ACS Nano·Axel HochstetterDavid W Inglis

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