Movies

  Simulations of molecular motors.

Frank in collaboration with Dr J-F. Chauwin (CIRCS post-doctoral fellow at CIRCS), and Prof Jorge José (director of CIRCS), developed simple mechanical models of molecular motors, firstly to model gliding-assay experiments, and then in order to understand their role in mitotic-spindle formation.
Spidle and Gliding Assay
The simulations here recreate attempt to model the work of Howard et al. (Nature, 1989). In their gliding assay experiment, they coated a microscope slide with kinesin (which we show as little green dots), causing the tail-domains to stick to the surface. A microtubule (the stick-like object) was then dropped onto the surface, and propelled along by the action of the motors.
Howard et al. studied the speed of this translation as a function of the density of motors attached to the slide, and found that it was more or less constant, over several orders of magnitude. Because the microtubule has a polarity, I have indicated the plus end in some of the newer movies. The kinesins try to move towards this end, which means the other (`minus') end leads.


Title: Spindle
m200-d100 (MPG, 6.6Mb)
Mitotic spindle, 200 microtubules, 100 dyneins. The microtubules are shown in red, with the plus ends indicated in blue (all colors are, of course, false).

m200-d500 (MPG, 1.8Mb)
Mitotic spindle, 200 microtubules, 500 dyneins. The microtubules are shown in red, with the plus ends indicated in blue (all colors are, of course, false).

m200-d1000 (MPG, 1.4Mb)
Mitotic spindle, 200 microtubules, 1000 dyneins. The microtubules are shown in red, with the plus ends indicated in blue (all colors are, of course, false).

m200-d2000 (MPG, 1.8Mb)
The mitotic spindle, as formed by motors, using 200 microtubules, and 2000 dyneins. The microtubules are shown in red, with the plus ends indicated in blue (all colors are, of course, false). No motors are shown in this movie. The white spheres at the center of the image represent the chromatin-coated latex spheres in the experiments of Heald et al., which provide an anchoring site for the kinesins.

m300-d1000 (MPG, 1.86Mb)
The mitotic spindle, this time with 300 microtubules, and only 1000 dyneins. Notice how the smaller ratio of dyneins to microtubules (compared to the movie above) results in a slower (and less symmetrical) convergence to a spindle-like structure.


Title: Gliding Assay
Sigma5 (MPG, 0.84Mb)
Low motor density (5 µm-2). This is about the minimum density at which we get consistent motion in our simulations, based on the parameters that we believe to be the best match to the physical behavior of the motors.

Sigma10 (MPG, 0.84Mb)
Intermediate motor density (10 µm-2). At this density, the microtubule is pretty securely anchored to the substrate, and moves relatively smoothly. The substrate is 20 µm square, while the microtubule is 10 µm in length. As you can see, the microtubule moves a distance equal to its own length. There are still some noticeable angular fluctuations.

Sigma100 (MPG, 0.09Mb)
High motor density. (100 µm-2) Notice how the angular deviations are much smaller at high motor density. The microtubule is rarely free, but is held by many dozens of motors, and therefore has less freedom.
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