Chromatin swelling drives neutrophil extracellular trap release

• Published in: Nature communications Vol. 9; no. 1; pp. 3767 - 13
• Main Authors: Neubert, Elsa, Meyer, Daniel, Rocca, Francesco, Günay, Gökhan, Kwaczala-Tessmann, Anja, Grandke, Julia, Senger-Sander, Susanne, Geisler, Claudia, Egner, Alexander, Schön, Michael P., Erpenbeck, Luise, Kruss, Sebastian
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.09.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 14/19; 14/3; 14/34; 14/63; 631/250/2504/223/1699; 631/337/100; 631/57; 631/80/82; 639/766/747; Atomic force microscopy; Biological activity; Cancer; Cell Death; Cell Membrane; Cell Shape; Chromatin; Chromatin - metabolism; Chromatin - ultrastructure; Cytology; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA - ultrastructure; Entropy; Evolutionary conservation; Expulsion; Extracellular Traps - metabolism; Fluorescence; Humanities and Social Sciences; Humans; Inflammatory diseases; Leukocytes (granulocytic); Leukocytes (neutrophilic); Material properties; Microscopy, Atomic Force; Microscopy, Fluorescence; Morphology; multidisciplinary; Neutrophils; Neutrophils - metabolism; Neutrophils - ultrastructure; Nuclear Envelope; Science; Science (multidisciplinary); Single-Cell Analysis; Swelling
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-06263-5

Neutrophilic 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. Neutrophilic granulocytes release their own DNA (NETosis) as neutrophil extracellular traps to capture pathogens. Here, the authors use time-resolved fluorescence and atomic force microscopy and reveal that NETosis is highly organized into three distinct phases with a clear point of no return defined by chromatin status.