Cell migration through three-dimensional confining pores: speed accelerations by deformation and recoil of the nucleus.
Marina Krause, Feng Wei Yang, Mariska Te Lindert, Philipp Isermann, Jan Schepens, Ralph J A Maas, Chandrasekhar Venkataraman, Jan Lammerding, Anotida Madzvamuse, Wiljan Hendriks, Joost Te Riet, Katarina Wolf
Author Information
Marina Krause: Department of Cell Biology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Feng Wei Yang: Department of Mathematics, School of Mathematical and Physical Sciences, University of Sussex, Falmer, Brighton BN1 9QH, UK.
Mariska Te Lindert: Department of Cell Biology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Philipp Isermann: Meinig School of Biomedical Engineering, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
Jan Schepens: Department of Cell Biology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Ralph J A Maas: Department of Cell Biology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Chandrasekhar Venkataraman: Department of Mathematics, School of Mathematical and Physical Sciences, University of Sussex, Falmer, Brighton BN1 9QH, UK.
Jan Lammerding: Meinig School of Biomedical Engineering, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
Anotida Madzvamuse: Department of Mathematics, School of Mathematical and Physical Sciences, University of Sussex, Falmer, Brighton BN1 9QH, UK.
Wiljan Hendriks: Department of Cell Biology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Joost Te Riet: Department of Tumor Immunology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Katarina Wolf: Department of Cell Biology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
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'.
