high-Coherence, ultraCold electron diffraction for molecular movies of membrane Proteins

ended

Imagine we could make movies of proteins in action. In this project, I propose to develop a unique, table-top setup based on the diffraction of ultracold electrons that does exactly that: make molecular movies of proteins, in particular of the important class of membrane proteins. This tool could revolutionize biochemistry, yielding an ultimate view of nature’s molecular machinery, and helping scientists to understand membrane-protein-related diseases and develop highly targeted medicines. A unique source, developed at the TU/e and based on the femtosecond photoionization of an ultracold gas, generates electron pulses that should in principle be sufficiently short, intense and coherent to enable electron diffraction on 2D crystals of membrane proteins. In this project I will evaluate the source’s capability to generate high-quality diffraction patterns from 2D crystals of e.g. hydrophobin and bacteriorhodopsin. Next, I will measure a sequence of such diffraction patterns in a pump-probe experiment, to obtain a molecular movie of the light-induced conformational change of bacteriorhodopsin. This will be the first protein molecular movie ever obtained on a table-top setup. In parallel, I will improve the source performance. Accelerating the electrons to higher energies (from 10 to above 100 keV), I can keep the sample in its native, aqueous environment inside a Liquid Cell, which strongly extends the applicability of the setup. Modifying the spatial and spectral properties of the ionization laser, I expect to be able to increase the number of electrons per pulse, allowing single-shot diffraction patterns, and to further increase transverse coherence, reducing the required crystal size. Finally, I will seek to improve the coherence of the source to the point where I can apply my experience in Coherent Diffractive Imaging to make molecular movies of a single protein, without crystallization, which is a holy grail in structural dynamics, all on a table-top setup.