Golden help to track fast biomolecular processes
Sjoerd Nooteboom defended his PhD thesis at the Department of Applied Physics and Science Education on April 9th.
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The human body is made up of trillions of cells, with each containing millions of biomolecules such as proteins and DNA. An incredible complex interplay of movements and interactions of these molecules ensures that cells function properly and that the body stays healthy. Some of these processes can take place over a timescale just a millionth of a second or even less. In his PhD research, PhD Sjoerd Nooteboom developed a method to study 'live' the fast processes of single biomolecules with a little help from gold nanoparticles.
Imagine you want to take a video of a falling star with a camera. To track how it moves, you need a camera with a high frame rate. This means that the exposure time will be so short that very little light is recorded per frame, and due to noise you will not get a clear image of the falling star.
To get the most detailed information possible about the behavior of biomolecules, researchers often look at an individual molecule and follow it by tracking its fluorescence signal in an optical microscope. They illuminate the molecule with a laser and measure the light it then emits with a camera.
This approach works well for most processes. However, when the biological process is very fast, the intensity of the light emitted by a molecule is too weak to measure.
To study the fastest movements and interactions of biomolecules, we need to increase the fluorescence intensity of the molecule.
Going for gold
In his PhD thesis, Sjoerd Nooteboom outlined how he used gold nanoparticles to help increase the fluorescence intensity of biomolecules.
When a fluorescent molecule gets very close to a nanoparticle, the fluorescence is increased by as much as a hundred fold. This way, it becomes possible to study biomolecules over very short timescales. This is equivalent to the case where it would be easy to video and track a falling star if it were a hundred times brighter.
Besides the total increase of the fluorescent signal, Nooteboom also investigated the effect that a gold nanoparticle has on the fluorescence process in terms of the colors that are emitted.
Furthermore, he investigated how hot the nanoparticles get during the measurements, as a result of the required laser excitation of the gold nanoparticles. This is important because too high a temperature can damage the biomolecules under study.
In the future, the developed methods can be applied to many different biomolecules. This way, researchers can gain a better understanding of how biomolecules behave on short timescales, and how that affects healthy and diseased cells.
This can eventually enable new developments in medicine, for example, for the development of new or personalized drugs.
Title of PhD-thesis: A Golden Key to Microseconds: Plasmon-Enhanced Single-Molecule Fluorescence for Ultrafast Biomolecular Dynamics. Supervisors: Peter Zijlstra and Menno Prins (TU/e).