Nanotechnology for biophysics: from single molecules towards synthetic cells

Speaker: Cees Dekker
Department:
Bionanoscience
Subject:
Nanotechnology for biophysics: from single molecules towards synthetic cells
Location: Lecture room E (TU Delft)
Date: 09-02-2017

Kristian Blom

After six months of following theoretical physics and astronomy courses for my minor, I was looking forward to hear something about nanobiology again. Therefore I took the opportunity to visit a seminar given by Cees Dekker for the quantum nanoscience department about nanotech nology for biophysics.

To break the ice between the applied physicists (audience) and the nanobiologist,  prof. Dekker started his talk with a quick review of his scientific career. In 1984 he started his career in solid state physics (which impressed the audience for sure) and over the years he got more and more fascinated by biophysics and nanobiology. Therefore he made the decision to switch from quantum physics to biophysics around 2000. In the past 15 years Prof. Dekker mainly focused on the study of cellular components using the top-down approach. For this kind of research nanotechniques are used to probe the biological cell at its most fundamental level; single biomolecules.

So what is nanotechnology? Specifically in the field of biophysics we can describe nanotechnology as a toolbox of instruments for studies at the single-atom and single-molecule level. A very famous example of this is the scanning tunneling microscope. Another example are the optical and magnetic tweezer with which you can measure the mechanical properties of DNA. Prof. Dekker explained the audience that with a magnetic tweezer you can coil up a DNA strand by applying an external rotating magnetic field to a bead with one end of a DNA molecule is attached. 

Currently the research group of prof. Dekker focuses on three main topics: Single-molecule biophysics of DNA and DNA-protein complexes, solid-state nanopores and its applications, and finally bacteria in nanostructures. I will discuss the former topic in a bit more detail by explaining one of the recent findings of  the Dekker group in this field.

isd
Figure 1 – Intercalation-induced Supercoiling of DNA (ISD) Source: Ganji, M.; Hyun Kim, S.; van der Torre, J.; Abbondanzieri, E.; Dekker, C. Nano Lett, 2016, 16 (7), pp 4699-4707

The subject of this recent finding is on DNA supercoiling, which is the over- (positively coiled) or under-winding (negatively coiled) of the DNA strand. Since supercoiling plays a very important role in biological processes such as DNA compaction, gene expression and DNA replication, it is very important for the cell to keep control of the supercoiling state of DNA. A specific kind of supercoiled DNA configuration is the plectoneme; a DNA helix which is coiled onto itself. By using an intercalating dye the Dekker group induced supercoils within a linear DNA molecule that was bound to a surface at its two ends. Thereafter they investigated the plectoneme position and dynamics using epifluorescence microscopy. What they found is that the observed plectoneme density and the nucleation and termination rates showed position-dependent variations. More specifically, they found a strong peak in the plectoneme density, nucleation and termination rate near one end of the DNA (see figure 2). As nucleation of a plectoneme requires a lot of bending energy, a locally region where the DNA is already bend a little bit (intrinsic curvature) by external structures (e.g. DNA-bound proteins) would significantly promote the formation and growth of a plectoneme at this site. Therefore the Dekker group inserted a 10-nucleotide mismatched sequence in the middle of the DNA strand. They observed that the plectoneme density showed a peak at the position of the mismatched sequence. So, as expected, flexible DNA bubbles promote the plectoneme formation.

dna-sequence-dependent-pinning-of-plectonemes
Figure 2 – DNA sequence-dependent pinning of plectonemes. (A) Plectoneme densities of 46 identical DNA molecules (thin lines) and their average (red thick line). (B) Averaged nucleation (orange) and termination (blue) rates observed. C) Averaged position-dependent plectoneme size distributions. Source: Ganji, M.; Hyun Kim, S.; van der Torre, J.; Abbondanzieri, E.; Dekker, C. Nano Lett, 2016, 16 (7), pp 4699-4707

My heart leapt for joy when prof. Dekker mentioned that a theoretical model will be made about the nucleation and termination of plectonemes. Although experimental data tells us more about the truth (if the experiment is done properly) than a theoretical model, I think you can only understand a physical phenomenon in the very detail when someone can explain it using the fundamental laws of nature. After this very interesting part of the talk prof. Dekker quickly went over the other two topics where is research group is interested in. At the very end someone from the audience asked if quantum mechanics plays a significant role in the functioning of a cell. The answer of prof. Dekker was that it isn’t that important for phenomenon in the cell (except for photosynthesis and energy conversion). This disappointed me a little bit, since one of my future plans is to use quantum mechanics to get a better understanding of the cell (therefore I will also follow quantum mechanics in the coming semester). But luckily not everything is discovered so far, so for me there is still hope that one day quantum mechanics will be an essential part of every cell biology course!

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