Beruflich Dokumente
Kultur Dokumente
Dept. of Chemistry & Biochemistry, Texas Tech University/ 2Dept. Of Chemical Engineering, Texas Tech University
Introduction
Results
Neurodegenerative Diseases
Alzheimers, Parkinson's, and Huntington
Progressive loss of neuronal function/muscular
dystrophy/problem in coordination.
Neurodegenerative diseases occur because of
mitochondrial dysfunction
oxidative stress, and
protein aggregation.
Figure 1: Microfluidic apparatus for recording muscular force production in C. elegans. (a) Schematic showing the
apparatus configuration including the chamber for housing worms, deformable pillar arrays, microscope objective for
visualizing pillar deflection and locomotion of C. elegans. The housing chamber is made of a non-permeable elastomeric
substrate (Polydimethylsiloxane) for experiments. (b) Schematic of a deflected pillar/sensor by section of worm body
(exaggerated image). (c) Image of a C. elegans in the microfluidic pillar apparatus deforming the sensors. (d) Scanning
electron microscope (SEM) pictures of the pillars.
Figure 4: Effect of cholinergic agonist levamisole (1mM) on muscle force production. (a)
Force production by C. elegans before treatment with drug (red: N =20, n = 3992), during
treatment with drug (green, N = 17, n = 3592) and during recovery after 4 hrs with food (black:
N = 14, n = 3142). Inset is comparison of median force and 95 percentile for each case. (b) C.
elegans before exposure, during exposure and during recovery after 4 hours.
Figure 2: Muscle force production in wild-type C. elegans (a) Images of the worm interacting with different pillars during
a locomotory episode. Maximum force is experienced by pillar 4 in the first image and by pillar 2 in the second and third
images. The dashed horizontal lines help easy visualization of the pillar deflection. Scale bar is 100 m. (b) Force profiles of
four pillars that the worm is interacting with during the episode. The arrows indicate the maximum force in frames (i)-(iii).
(c) Force signature of a worm constructed by picking up only the maximum force experienced (among all pillars in
interaction) at each frame. Colors represent the contribution of the pillars in construction of the force signature in each frame.
(d) A typical representation of the force data in terms of cumulative probability distribution. (e) A flow chart of cumulative
distribution function estimation.
Muoz-Lobato et. Al. Antioxidants & Redox Signaling,
20(2), 2014
Figure 5: Muscle force production of Parkinsons model. Force production by wild type C.
elegans (red: N =20, n = 3992) and Parkinsons model unc-119 (ed3) III; pkls2386 [Punc54::alpha-synuclein::YFP, unc-119(+)] IV as a model organism for Parkinson's disease (green,
N = 21, n = 2483).
Conclusion
The Nemaflex device can reliably evaluate the strength of C.
elegans/mutants.
The protein aggregation in C. elegans Parkinsons models
produces significantly lower forces.