Intricacies of scientific models

I have always been a sucker for fancy and intricate scientific devices.  I don’t want to say instruments, because that would imply electronic equipment.  Although even there, if it has to do with imaging cells, I’m in!  But I am referring more to items that you can actually touch and interact with, especially on a miniature scale.

I remember when I was in elementary school, I was notified of our first science fair.  I told my mom that we have to go to a bookstore and find some material for project ideas.  I came across a book that made the most sense.  It was thick, with a large selection of experiments appropriate for an elementary school student.  It included things like mixing of hydrophilic and hydrophobic fluids, potato electricity and electromagnetism.  I was ready to go and start deciding on the best project.  But then, a small and skinny book caught my attention.  On the cover, it had a complex glass structure, containing two vessels of brightly colored water, that was made to create a DIY fountain.  I could not resist.  When I came home and actually started reading, it turned out that the instrument consisted of about 6-8 glass pieces that had to be custom made to order.  Well, that project went out the window.  But I still kept coming back to this book and could not leave this idea alone.  I ended up making a non-functioning structural model of this device for the following science fair, which was not sufficient to quench my thirst, but it was better than nothing…

Jumping forward more than a decade, in graduate school while I was working on maturation of neurons, I accidentally came across a small microfluidic device that could direct the growth of neuronal axons.  I did not need it for my project at the time, but I was hooked.  I actually started looking for a way to find use for it and ended up building my project around the use of these devices, rather than the other way around.  A preliminary version of the paper can be found here.

Finally, at my previous job I found a better method to model multiple sclerosis in vitro (in a dish).  Over the past decade, more and more evidence has shown that plating cells on a flat surface does not accurately recapitulate all of their functions.  While it can be sufficient for studying a lot of functions, such as cell biochemical signaling, more complex phenomena require more complex models.  In multiple sclerosis, the body’s immune system attacks and destroys cells called oligodendrocytes, which insulate neuronal connections to improve electrical signal conduction.  While oligodendrocytes can be plated in a flat dish, as they differentiate and mature, they put out extensive membranes that are meant to wrap around neuronal axons.  But they have nothing to wrap.  It so happened that a few weeks before leaving my postdoctoral fellowship position, I attended a seminar where a renowned scientist from UCSF presented a novel system of using synthetic nanofibers to act in place of axons.  My brain started firing.  I ended up incorporating this model into my next project at my new job and made an artwork inspired by a real image I took in the lab.  Here I switched up the colors a bit (upper right cell) to make it more interesting and added the blue channel that was not captured, but could be easily inferred based on the location of cell bodies.  The blue channel shows cell nuclei.

This week I came across a very recent paper, where the authors devised a new miniature culture model to study Alzheimer’s disease.  Unlike the previous methods of studying cell function in vitro where 1-2 cell types were used, this model allows incorporation of all 3 major human brain cell types.  These include neurons, astrocytes and microglia, allowing the scientist to capture all major functions involved in Alzheimer’s.  Namely, beta-amyloid accumulation, phosphorylated tau formation, hyperactivation of glial cells, neuroinflammation and neuronal loss.

After seeing this model, my hands started itching to recreate it as an artistic rendering.  🙂

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