When nano first met biology
by Xun Lu
Lysozyme is an enzyme that helps to protect us from getting bacterial infections because it can degrade and utilize the sugars in the bacterial cell wall. A good source of lysozyme is human tears.
A single lysozyme molecule is so small that one can’t really see it with the naked eye or even under the most powerful microscope. However, scientists at UC Irvine now can use an electronic chip to record the dynamic motions of a lysozyme molecule hydrolyzing its favorite substrate in REAL TIME. It’s like using an iPod to monitor your pace during a workout except that the iPod only gives you an average rate. In contrast, this electronic chip shows the pace of a lysozyme molecule every 10 micro-seconds throughout its entire workout. Just as we hold the iPod to monitor our pace, the lysozyme molecule has to stick to the electronic chip so that its pace can be measured.
So, what is this magic electronic chip? Actually, it’s not something that you are totally unfamiliar with. I am sure you have heard of nanotechnology. Scientists roll up a single layer of carbon atoms into a tube that is tens of thousands times thinner than a human hair. These nanotubes are then placed on a chip to make electronic transistors and wires. This technology has been around for years, and one day may it be used to make super-computers as skinny as your current laptop.
The carbon nanotubes will also save energy for our planet. Check out the use of nanotubes in desalination projects, for example. In the present, the nanotubes already have been used to study chemical reactions, and the technology is being applied to biological systems right now!
The Weiss and Collins groups in the Department of Chemistry at UC Irvine describe the use of nanocircuits to study enzymatic reactions in a recent paper published in Science. A single biological molecule, like lysozyme, is tethered to a nanotube by a chemical linker. The dynamic motions of the enzyme, when carrying out the enzymatic reaction, cause fluctuations in the conductance and hence the current flowing through the nanotube. By monitoring the current change over time, one can “watch” a single lysozyme molecule hydrolyze the glycosidic bonds of its substrates, either a synthetic linear substrate or a bacterial cell wall (a cross-linked substrate). It turns out that lysozyme had an easier time biting the softer synthetic candy (linear substrate) compared to the tough bacterial cell wall (cross-linked substrate). So, the technique can be used to distinguish different substrates. The sensitivity of the technique makes the nanocircuit a good bio-sensor.
The fine time resolution (micro-seconds) is the exciting part of this nanotechnology, since more details are being revealed. By examining the enzymatic reactions in a new way, we gain a better understanding of the chemical mechanisms.
Choi, Y., Moody, I., Sims, P., Hunt, S., Corso, B., Perez, I., Weiss, G., & Collins, P. (2012). Single-Molecule Lysozyme Dynamics Monitored by an Electronic Circuit Science, 335 (6066), 319-324 DOI: 10.1126/science.1214824
Choi, Y, Moody, I. S., Sims,, P. C., Hunt, S. R., Corso, B. L., Seitz, D. E., Blaszcazk, L. C., Collins, P. G., & Weiss, G. A. (2012). Single-molecule dynamics of lysozyme processing distinguishes linear and cross-linked peptidoglycan substrates. J. Am. Chem. Soc. 134, 2032–2035. DOI: 10.1021/ja211540z