Department of Physics, AlbaNova University Center, Stockholm University, SE-106 91, Stockholm, Sweden.
Institut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076, Tübingen, Germany.
Nat Commun. 2022 Sep 21;13(1):5528. doi: 10.1038/s41467-022-33154-7.
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 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.
兆赫兹自由电子激光（XFEL）具有兆赫兹重复率，可以为生物大分子溶液的结构动力学提供新的见解。然而，非常高的剂量率可能会由于辐射损伤而导致束致动力学和结构变化。在这里，我们使用欧洲 XFEL 的兆赫兹 X 射线光子相关光谱学（MHz-XPCS）探测密集抗体蛋白（Ig-PEG）溶液的动力学。通过改变总剂量和剂量率，我们确定了一个测量蛋白质在其第一配位壳内运动的范围，量化了 XFEL 诱导的效应，如驱动运动，并绘制出团聚动力学的范围。结果表明，在 10 μs 时间窗口内，平均剂量率低于 1.06 kGy μs 时，有可能在束致聚集发生之前捕捉到蛋白质动力学。我们将这种方法称为聚集前相关，并证明 MHz-XPCS 弥合了生物样品测量技术中的一个重要时空差距。
