title: Microfluidics-based single cell analysis reveals drug-dependent motility changes in trypanosomes.
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.
authors.affiliation: Department of Chemistry, University of Basel, 4056 Basel, Switzerland. thomas.pfohl@unibas.ch.
authors.forename: Axel
authors.initials: A
authors.lastname: Hochstetter
authors.forename: Eric
authors.initials: E
authors.lastname: Stellamanns
authors.forename: Siddharth
authors.initials: S
authors.lastname: Deshpande
authors.forename: Sravanti
authors.initials: S
authors.lastname: Uppaluri
authors.forename: Markus
authors.initials: M
authors.lastname: Engstler
authors.forename: Thomas
authors.initials: T
authors.lastname: Pfohl
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D003847:Deoxyglucose / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation*; D004867:Equipment Design; D005976:Glutaral / Q000494:pharmacology; D056656:Lab-On-A-Chip Devices; D008853:Microscopy; D052898:Optical Tweezers; D059010:Single-Cell Analysis / Q000295:instrumentation*; D013498:Suramin / Q000494:pharmacology; D013997:Time Factors; D014346:Trypanosoma brucei brucei / Q000166:cytology* / Q000187:drug effects*
chemical_list: D013498:Suramin; D003847:Deoxyglucose; D005976:Glutaral