Chromatin swelling drives neutrophil extracellular trap release

• DOI: 10.1038/s41467-018-06263-5
• Publication Date: 2018-09-10T13:41:35Z
• Authors: Elsa Neubert; Daniel Meyer; Francesco Rocca; Gökhan Günay; Anja Kwaczala-Tes...; Julia Grandke; Susanne Senger-Sa...; Claudia Geisler; Alexander Egner; Michael P. Schön; Luise Erpenbeck; Sebastian Kruss
• Keywords: 0301 basic medicine; Cell Death; Neutrophils; Nuclear Envelope; Science; Entropy; Q; Cell Membrane; 610; DNA; Microscopy, Atomic Force; Extracellular Traps; Article; Chromatin; 3. Good health; 03 medical and health sciences; Microscopy, Fluorescence; Humans; Single-Cell Analysis; Cell Shape

AbstractNeutrophilic granulocytes are able to release their own DNA as neutrophil extracellular traps (NETs) to capture and eliminate pathogens. DNA expulsion (NETosis) has also been documented for other cells and organisms, thus highlighting the evolutionary conservation of this process. Moreover, dysregulated NETosis has been implicated in many diseases, including cancer and inflammatory disorders. During NETosis, neutrophils undergo dynamic and dramatic alterations of their cellular as well as sub-cellular morphology whose biophysical basis is poorly understood. Here we investigate NETosis in real-time on the single-cell level using fluorescence and atomic force microscopy. Our results show that NETosis is highly organized into three distinct phases with a clear point of no return defined by chromatin status. Entropic chromatin swelling is the major physical driving force that causes cell morphology changes and the rupture of both nuclear envelope and plasma membrane. Through its material properties, chromatin thus directly orchestrates this complex biological process.