Chromatin swelling drives neutrophil extracellular trap release

Elsa Neubert, Daniel Meyer, Francesco Rocca, Gökhan Günay, Anja Kwaczala-Tessmann, Julia Grandke, Susanne Senger-Sander, Claudia Geisler, Alexander Egner, Michael P. Schön, Luise Erpenbeck () and Sebastian Kruss ()
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Elsa Neubert: Goettingen University
Daniel Meyer: Göttingen University
Francesco Rocca: Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)
Gökhan Günay: Goettingen University
Anja Kwaczala-Tessmann: Goettingen University
Julia Grandke: Goettingen University
Susanne Senger-Sander: Goettingen University
Claudia Geisler: Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)
Alexander Egner: Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)
Michael P. Schön: Goettingen University
Luise Erpenbeck: Goettingen University
Sebastian Kruss: Göttingen University

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-06263-5

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