CHEMICAL AND GENETIC SCREENING APPLICATIONS OF A MICROFLUIDIC ELECTROTAXIS ASSAY USING NEMATODE CAENORHABDITIS ELEGANS

Abstract

Combining the nematode Caenorhabditis elegans with novel microfluidic technology has produced a phenotypic movement assay that is at once rapid, sensitive, and low-cost. The method is based on the neurophysiologic phenomenon of worms exhibiting robust, continuous, directed locomotion in response to mild electric fields inside a microchannel. As we demonstrate with the studies reported herein, our microfluidic electrotaxis platform is a unique tool for studying the effects of environmental and genetic manipulations on C. elegans’ movement behaviour, which in turn indicates the state of the organism’s neuronal and muscular systems. In one initiative to develop an inexpensive biosensor, we use the setup to measure the response of worms to common environmental pollutants. Results indicate that worms’ electrotactic swimming behaviour is particularly susceptible to metal salts. A comparison with traditional assays measuring fecundity, growth, and lifespan reveals that electrotactic speed shows a comparable level of sensitivity as a toxicity endpoint. Another study demonstrates that worms expressing a mutant form of α-synuclein, a familial Parkinson’s disease-related protein, show deficits in electrotactic swimming speed that coincide with dopaminergic neuron damage. We further show that both the electrotaxis and neuronal phenotypes can be ameliorated by treatment with curcumin, a putative neuroprotective agent. We have also used the platform to investigate the effects of other environmental and genetic stresses on electrotactic behaviour. Our findings indicate that the response can withstand many different insults but is affected by stresses that induce the mitochondrial and ER unfolded protein responses, which themselves play roles in preserving electrotactic swimming behaviour alongside the heat shock response. These data expand our knowledge of how the motor output component of C. elegans’ electrotactic response is perturbed by environmental and genetic manipulations, and also support the utility of microfluidic electrotaxis as a functional output of nematode locomotory circuits in a multitude of contexts.