Sunday, October 16, 2016

Peering Into Our Machines

Would it be an overstatement to say that cellular biology is the most amazing thing in the universe?  It is the basis of all life.  Zoomed in.  Right down to the atomic level, where the elements are combining and recombining, swapping electrons, trading polarities.

I was fortunate to have been able to teach basic science at the high school level without any real university study.  I was able to brush up enough to pass the basic exams for credentialing.  I sometimes felt bit fraudulent - I really didn't have the proper training.  But they needed science teachers, and I was able to pass the basic requirements.

Science is like a giant puzzle - the chemistry, the physics, the biomes, the geology - it all fits together.  And you can always go deeper.  Centuries ago, a single individual could reasonably learn all there was to know about the natural world.  Yet today, our scientific knowledge has become so deep and specialized that no one could possibly hope to know everything even in one's own sub-sub discipline.

Even if I had majored in biology I don't think I would have gotten into anything very meaty until grad school.  Even then, I would only be scratching the surface of the cell.

Today I happened upon a field I honestly wasn't quite aware exited: biophysics.  As it's name implies, it is a field that seeks to bridge biology and physics, using our knowledge of both to better understand the fundamental processes and mechanics at work.

Something had always puzzled me about cellular mechanics is how in the heck we have actually made the discoveries that we have.   How did we learn the shape, structure, and operation of organelles like mitochondria, chloroplasts, or ribosomes?  How the heck were we able to determine how Rna transcription was taking place outside the nucleus?

I used to show my students the famous digitally animated animated short film "The Inner Life of the Cell", a collaboration between Xvivo studio and Harvard.  Created in 2006, it takes the viewer on an amazing tour of some of the basic operations of animal and plant cells.  The animators worked with scientists at Harvard's Molecular and Cellular Biology to create the most scientifically accurate representations possible - with the obvious concessions for things like clarity and illumination.  But allows one to visualize what it must be like to see all this stuff in action.

However, without a deeper understanding of the work involved, one's jaw is left on the floor, pondering how it is they could possibly know this stuff.  How is it that they discovered what kinesin proteins likely look like as they make their way down a microtubule, a giant vesicle in tow?

I know that these structures are incredibly tiny, and you simply can't see them at work.  Watson and Crick's discovery of the double helix only came after an analysis of Rosalin Franklin's resolution of DNA molecules through Xray crystallography.  Thats a far cry from what you can see being put forth in the film.

But like I said, I'm no expert.  I assume theres some kind of dyeing and chemical inference going on, all via very complex and painstaking analysis of extremely isolated samples.  But how exactly.  Would I never learn without attending a graduate seminar at university?

Thank to google, I came closer in my understanding tonight.  I found this article, part of a lecture on Molecular Machinery on the Institute of Physics website.  It's all rather complex and a bit much to try to go into here.  I encourage readers to check it out for themselves.  But I did enjoy mention of a particle of gold being used to demonstrate the process by which molecules can be transported throughout the cell.  One of the most astonishing portions of the Inner Life film is indeed that little protein that seems uncannily to be "walking" along a microtubule.  Well, this seems a good descrition of how they can show that process:
 The 40 nm gold bead scatters light very efficiently and the position of its centroid in a dark-field image can be fitted with nanometre resolution, even with frame rates close to 10 kHz. This small label exerts much less drag than the fluorescently labelled actin filaments (microns long) that were first used to prove that F1-ATPase is a rotary machine (see ‘Biological Energy’ Lecture 2). Combined with the fast video rates, this permits measurements with submillisecond time resolution that reveal substeps in the rotation of the stalk (rotor).

An illustration is helpfully provided.  As you can see, the gold bead is held in place, attached right to that little protein!  Marvelous!

So, it had been a while since I checked in to see what the Xvivo animation studio has been up to.  The Inner Cell was produced nearly ten years ago.  Both molecular biology and computer graphic design have surely improved greatly since then.  Boy, have they.   Their newer work is absolutely stunning.  I found this video of their work.
I'm especially impressed with the attempt to portray the stochaistic, or randomness with which the molecules bounce around against each other, jostling and jigging until their polarities match up and their function can begin.  I look forward to viewing more of their videos.  The future is just incredible.

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