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Nat Commun. 2018 Sep 14;9(1):3767. doi: 10.1038/s41467-018-06263-5.

Chromatin swelling drives neutrophil extracellular trap release.

Author information

1
Department of Dermatology, Venereology and Allergology, University Medical Center, Goettingen University, Göttingen, 37075, Germany.
2
Institute of Physical Chemistry, Göttingen University, Göttingen, 37077, Germany.
3
Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, 37073, Germany.
4
Optical Nanoscopy, Laser-Laboratorium Göttingen e.V., Göttingen, 37077, Germany.
5
Lower Saxony Institute of Occupational Dermatology, University Medical Center Göttingen and University of Osnabrück, Göttingen, 37075, Germany.
6
Department of Dermatology, Venereology and Allergology, University Medical Center, Goettingen University, Göttingen, 37075, Germany. luise.erpenbeck@med.uni-goettingen.
7
Institute of Physical Chemistry, Göttingen University, Göttingen, 37077, Germany. skruss@uni-goettingen.de.
8
Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, 37073, Germany. skruss@uni-goettingen.de.

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.

PMID:
30218080
PMCID:
PMC6138659
DOI:
10.1038/s41467-018-06263-5
[Indexed for MEDLINE]
Free PMC Article

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