Cell migration through three-dimensional confining pores: speed accelerations by deformation and recoil of the nucleus
| Autor: | Anotida Madzvamuse, Philipp Isermann, Jan Schepens, Mariska te Lindert, Chandrasekhar Venkataraman, Feng Wei Yang, Wiljan Hendriks, Joost te Riet, Ralph J. A. Maas, Marina Krause, Katarina Wolf, Jan Lammerding |
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| Rok vydání: | 2019 |
| Předmět: |
Materials science
chromatin condensation Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] Acceleration Corrections nuclear shape change General Biochemistry Genetics and Molecular Biology Biophysical Phenomena 03 medical and health sciences Mechanobiology 0302 clinical medicine Recoil All institutes and research themes of the Radboud University Medical Center Cell Movement Cell Line Tumor medicine Humans Softening speed oscillation 030304 developmental biology Cell Nucleus 0303 health sciences Other Research Radboud Institute for Health Sciences [Radboudumc 0] Cell Cycle Force spectroscopy Cell migration Articles migration in confinement Chromatin medicine.anatomical_structure 030220 oncology & carcinogenesis Biophysics tumour cell Interphase Collagen General Agricultural and Biological Sciences Nucleus Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] Lamin Research Article |
| Zdroj: | Philosophical Transactions-Royal Society. Biological Sciences, 374 Philosophical Transactions of the Royal Society B: Biological Sciences Philosophical Transactions-Royal Society. Biological Sciences, 374, 1779 |
| ISSN: | 0962-8436 |
| Popis: | Directional cell migration in dense three-dimensional (3D) environments critically depends upon shape adaptation and is impeded depending on the size and rigidity of the nucleus. Accordingly, the nucleus is primarily understood as a physical obstacle; however, its pro-migratory functions by stepwise deformation and reshaping remain unclear. Using atomic force spectroscopy, time-lapse fluorescence microscopy and shape change analysis tools, we determined the nuclear size, deformability, morphology and shape change of HT1080 fibrosarcoma cells expressing the Fucci cell cycle indicator or being pre-treated with chromatin-decondensating agent TSA. We show oscillating peak accelerations during migration through 3D collagen matrices and microdevices that occur during shape reversion of deformed nuclei (recoil), and increase with confinement. During G1 cell-cycle phase, nucleus stiffness was increased and yielded further increased speed fluctuations together with sustained cell migration rates in confinement when compared to interphase populations or to periods of intrinsic nuclear softening in the S/G2 cell-cycle phase. Likewise, nuclear softening by pharmacological chromatin decondensation or after lamin A/C depletion reduced peak oscillations in confinement. In conclusion, deformation and recoil of the stiff nucleus contributes to saltatory locomotion in dense tissues.This article is part of a discussion meeting issue ‘Forces in cancer: interdisciplinary approaches in tumour mechanobiology’. |
| Databáze: | OpenAIRE |
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