This work has “Gold” OA status. This means it is published in an Open Access journal that is indexed by the DOAJ.
Resolving molecular diffusion and aggregation of antibody proteins with megahertz X-ray free-electron laser pulses
Mario Reiser,Anita Girelli,Anastasia Ragulskaya,Sudipta Das,Sharon Berkowicz,Maddalena Bin,Marjorie Ladd-Parada,Mariia Filianina,Hanna-Friederike Poggemann,Nafisa Begam,Mohammad Sayed Akhundzadeh,Sonja Timmermann,Lisa Randolph,Yuriy Chushkin,Tilo Seydel,Ulrike Boesenberg,Jörg Hallmann,Johannes Möller,Angel Rodriguez-Fernandez,Robert Rosca,Robert Schaffer,Markus Scholz,Roman Shayduk,Alexey Zozulya,Anders Madsen,Frank Schreiber,Fajun Zhang,Fivos Perakis,Christian Gutt
Powered by Citationsy*
Reiser, M., Girelli, A., Ragulskaya, A., Das, S., Berkowicz, S., Bin, M., Ladd-Parada, M., Filianina, M., Poggemann, H.-F., Begam, N., Akhundzadeh, M. S., Timmermann, S., Randolph, L., Chushkin, Y., Seydel, T., Boesenberg, U., Hallmann, J., Möller, J., Rodriguez-Fernandez, A., … Gutt, C. (2022). Resolving molecular diffusion and aggregation of antibody proteins with megahertz X-ray free-electron laser pulses. Nature Communications, 13(1). https://doi.org/10.1038/s41467-022-33154-7
Full Text at PublisherAccess via your InstitutionCite this on CitationsyOpen in Google ScholarVisualize on Litmaps
Abstract X-ray free-electron lasers (XFELs) with megahertz repetition rate can provide novel insights into structural dynamics of biological macromolecule solutions. However, very high dose rates can lead to beam-induced dynamics and structural changes due to radiation damage. Here, we probe the dynamics of dense antibody protein (Ig-PEG) solutions using megahertz X-ray photon correlation spectroscopy (MHz-XPCS) at the European XFEL. By varying the total dose and dose rate, we identify a regime for measuring the motion of proteins in their first coordination shell, quantify XFEL-induced effects such as driven motion, and map out the extent of agglomeration dynamics. The results indicate that for average dose rates below 1.06 kGy μs −1 in a time window up to 10 μs, it is possible to capture the protein dynamics before the onset of beam induced aggregation. We refer to this approach as correlation before aggregation and demonstrate that MHz-XPCS bridges an important spatio-temporal gap in measurement techniques for biological samples.