학술논문
Resolving molecular diffusion and aggregation of antibody proteins with megahertz X-ray free-electron laser pulses
Document Type
Working Paper
Author
Reiser, Mario; Girelli, Anita; Ragulskaya, Anastasia; Das, Sudipta; Berkowicz, Sharon; Bin, Maddalena; Ladd-Parada, Marjorie; Filianina, Mariia; Poggemann, Hanna-Friederike; Begam, Nafisa; Akhundzadeh, Mohammad Sayed; Timmermann, Sonja; Randolph, Lisa; Chushkin, Yuriy; Seydel, Tilo; Boesenberg, Ulrike; Hallmann, Jörg; Möller, Johannes; Rodriguez-Fernandez, Angel; Rosca, Robert; Schaffer, Robert; Scholz, Markus; Shayduk, Roman; Zozulya, Alexey; Madsen, Anders; Schreiber, Frank; Zhang, Fajun; Perakis, Fivos; Gutt, Christian
Source
Nat Commun 13, 5528 (2022)
Subject
Language
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 $1.06\,\mathrm{kGy}\mathrm{\mu s}^{-1}$ in a time window up to $10\,\mathrm{\mu s}$, 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.
Comment: 22 pages, 6 figures
Comment: 22 pages, 6 figures