So what is it that I actually do?
A question we all should ask ourselves occasionally, I suppose. My primary role is as an experimental biophysicist, meaning that I do experiments using techniques developed in the field of physics (more on those shortly) to study biological molecules, specifically proteins.
How do I do it?
In my current project, I use a method called “optical trapping”, aptly named because using this technique it is possible to hold and manipulate objects using light. I had heard about the possibility of using light to hold objects many years before, and always thought the concept was quite intriguing. Before you get any ideas about levitating cats using lamps, though, let me explain.
First of all, the light used to create an optical trap should come from a laser, meaning that compared to the light that comes from a typical white lightbulb, which actually contains all of the colours, laser light only contains one colour. Secondly, the light is coherent (meaning that all of the light waves are synchronised with each other).
If we take a laser beam and focus it down to a very small spot, in the place where the spot is smallest we have created an optical trap. This can obviously be dangerous, so please don’t try it at home. The trap is formed because light has momentum, just like any moving object. You can’t feel it hitting your own skin but if something is small enough, it will experience this force on a significant level. This momentum pushes objects into the most intense part of the light beam (which is also the most focussed part), as long as they are within a certain size range and the light can pass through them.
Using optical trapping, it is possible to trap objects ranging from single atoms [1] up to a few hundred microns [2]. If you can then move the laser beam, for example by reflecting it using a moveable mirror, then you have the ability to not only hold, but also to move the trapped object.
The force needed to do this is very small, on the order of pico-Newtons (so 0.000000000001 of a Newton, or 0.000000000001 times the force you would feel if a small apple fell on your head from a tree). Conveniently, however, this is exactly the force range that is relevant in many biological processes [1,3], including the forces that bacteria use to move [4], the forces that hold protein molecules together [1,5,6] and the forces that must be applied to stretch DNA [7]. Add a second laser beam and you can hold an object in place while applying a force to it using the other laser beam. Now you can stretch a biological molecule.
Ok, but why do I want to measure forces in biological molecules?
Well, it might sound silly, but the problem with studying most biological molecules is that they are quite small. So small, in fact, that we can’t see them clearly even with very powerful light microscopes (you have to use other techniques such as X-rays or electron beams, but I won’t go into those now). An easy and intuitive way to overcome this limitation is to use methods that allow us to “feel” them. Imagine you have a loosely knotted piece of string but you don’t know how many knots there are in it. You close your eyes and hold the string between two hands and pull on it. Every time you undo a knot, you feel the sudden increase in the length of the string. If you keep pulling until the string feels taut, and you count how many times you felt a sudden increase in length, you know how many knots there were. This is exactly what I use optical trapping for, except instead of knots on a string, I’m pulling apart a protein molecule and by measuring how many knots there were and how far apart they were, I get an idea of the original shape of the protein.
I’m still not answering the question, am I? Well, in addition to being able to get some idea of the structure of the protein molecule, I also measure the forces that are holding it together and the forces it needs to move, which is how many proteins do their jobs in our bodies. There are proteins that open and close to trap and release other proteins [8], proteins which can ‘walk’ along tracks inside cells carrying cargo from one place to another [9, 10], and proteins which act as doorways which open and close between the inside of a cell and the outside [11] to name just a few.
Using optical trapping, we can watch these things happening and in doing so, learn how they work. This is essential not only for gaining an understanding of how living things function, but also for the development of drugs which can specifically target certain proteins without damaging others.
[1] http://www.pnas.org/content/94/10/4853.short
[2] https://www.osapublishing.org/oe/abstract.cfm?uri=oe-17-19-16731
[3] https://www.nature.com/articles/nmeth.1218
[4] https://www.nature.com/articles/338514a0
[5] https://www.nature.com/articles/ncomms10848
[6] http://pubs.rsc.org/en/content/articlelanding/2013/sm/c3sm51439k/unauth#!divAbstract
[7] https://www.sciencedirect.com/science/article/pii/S0959440X15000901
[8] http://www.pnas.org/highwire/filestream/603888/field_highwire_adjunct_files/0/SM01.mpg
[9] https://youtu.be/gbycQf1TbM0
[10] http://pdb101.rcsb.org/motm/64
[11] http://pdb101.rcsb.org/motm/107