How can you push DNA through Jello? (What is biophysics? #1)

An introduction to the series: It’s easy to write that biophysics is the intersection of biology and physics, but this is a minimal and cryptic description. We could elaborate, and describe biophysics as the study of how living things use physical forces to shape themselves, how we can harness physical processes for technological ends, and how universal physical laws dictate how life works. This description is still rather short and abstract, and so I’ve written a 300-page, illustrated popular science book coming out in Feb. 2022 that explores this fascinating subject with abundant examples. (Publisher’s page; my description.)

I’ve also thought that presenting questions is another way to highlight what biophysicists tackle, and so I decided to write a series of posts each posing one question, with a simple illustration and just a few words about the answer (or what we know of the answer). Most of the questions I’ve planned touch on topics I’ve written about in my book, but several do not. Here’s the first!

How can you push DNA through Jello?

(And why would you want to?)

A gel is a mesh of long, stringy molecules, crisscrossing each other amid a liquid backdrop, typically water. Gelatin (such as Jello) is a household example. DNA is also a long, chain-like molecule, and to move through a gel it needs to snake its way through the porous landscape. An electric field can push it along: One of the fundamental physical properties of DNA is a strong electrical charge. It turns out that in a gel, the speed of a DNA molecule driven by an electric field depends on the molecule’s length. Longer strands have a harder time making progress through the pores; shorter ones move faster. This may seem obvious, but it’s not the case in a simple fluid like water; there, the speeds of different lengths of DNA are all very similar.

An electric field, therefore, will push DNA through a gel, and shorter strands will travel farther in a given amount of time. This allows us to separate strands based on length. Some of the techniques we use to read DNA sequences, the first step in deciphering the messages they encode, involve breaking DNA into fragments, copying the fragments, and separating them by size. In the classic method of Sanger sequencing, for example, we can determine the “letter” of the code that’s at the end of a strand, so if we know that strands of length 10 end in “A” and length 11 in “G” and length 12 in “T”, we know what the sequence was “…AGT…”

There are now many other clever and creative DNA sequencing methods that, even if they don’t push DNA through gels, make use of its physical properties in other ways. (See Chapter 13: How We Read DNA!)

Stay tuned for Question 2…

Time is in short supply, so my hope for the posts in this series is to keep them short and to keep the illustrations simple. Nonetheless, the painting above took me eight tries until I had something I didn’t think was awful. Hopefully I’ll be faster next time!

— Raghuveer Parthasarathy; December 17, 2021