TY - JOUR
T1 - Phenotyping of the thrashing forces exerted by partially immobilized
T2 - C. elegans using elastomeric micropillar arrays
AU - Sofela, Samuel
AU - Sahloul, Sarah
AU - Stubbs, Christopher
AU - Orozaliev, Ajymurat
AU - Refai, Fathima Shaffra
AU - Esmaeel, Abdelhady Mostafa
AU - Fahs, Hala
AU - Abdelgawad, Mohamed Omar
AU - Gunsalus, Kristin C.
AU - Song, Yong Ak
N1 - Publisher Copyright:
This journal is © The Royal Society of Chemistry.
PY - 2019/11/7
Y1 - 2019/11/7
N2 - As a simple model organism, C. elegans plays an important role in gaining insight into the relationship between bodily thrashing forces and biological effects, such as disease and aging, or physical stimuli, like touch and light. Due to their similar length scale, microfluidic chips have been extensively explored for use in various biological studies involving C. elegans. However, a formidable challenge still exists due to the complexity of integrating external stimuli (chemical, mechanical or optical) with free-moving worms and subsequent imaging on the chip. In this report, we use a microfluidic device to partially immobilize a worm, which allows for measurements of the relative changes in the thrashing force under different assay conditions. Using a device adapted to the natural escape-like coiling response of a worm to immobilization, we have quantified the relative changes in the thrashing force during different developmental stages (L1, L3, L4, and young adult) and in response to various glucose concentrations and drug treatment. Our findings showed a loss of thrashing force following the introduction of glucose into a wild type worm culture that could be reversed upon treatment with the type 2 diabetes drug metformin. A morphological study of the actin filament structures in the body wall muscles provided supporting evidence for the force measurement data. Finally, we demonstrated the multiplexing capabilities of our device through recording the thrashing activities of eight worms simultaneously. The multiplexing capabilities and facile imaging available using our device open the door for high-throughput neuromuscular studies using C. elegans.
AB - As a simple model organism, C. elegans plays an important role in gaining insight into the relationship between bodily thrashing forces and biological effects, such as disease and aging, or physical stimuli, like touch and light. Due to their similar length scale, microfluidic chips have been extensively explored for use in various biological studies involving C. elegans. However, a formidable challenge still exists due to the complexity of integrating external stimuli (chemical, mechanical or optical) with free-moving worms and subsequent imaging on the chip. In this report, we use a microfluidic device to partially immobilize a worm, which allows for measurements of the relative changes in the thrashing force under different assay conditions. Using a device adapted to the natural escape-like coiling response of a worm to immobilization, we have quantified the relative changes in the thrashing force during different developmental stages (L1, L3, L4, and young adult) and in response to various glucose concentrations and drug treatment. Our findings showed a loss of thrashing force following the introduction of glucose into a wild type worm culture that could be reversed upon treatment with the type 2 diabetes drug metformin. A morphological study of the actin filament structures in the body wall muscles provided supporting evidence for the force measurement data. Finally, we demonstrated the multiplexing capabilities of our device through recording the thrashing activities of eight worms simultaneously. The multiplexing capabilities and facile imaging available using our device open the door for high-throughput neuromuscular studies using C. elegans.
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U2 - 10.1039/c9lc00660e
DO - 10.1039/c9lc00660e
M3 - Article
C2 - 31576392
AN - SCOPUS:85073667043
SN - 1473-0197
VL - 19
SP - 3685
EP - 3696
JO - Lab on a Chip
JF - Lab on a Chip
IS - 21
ER -