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Cell migration through 3D confining pores: speed accelerations by deformation and recoil of the nucleus
Version 2 2023-06-12, 09:07
Version 1 2023-06-09, 17:54
journal contribution
posted on 2023-06-12, 09:07 authored by Marina Krause, Feng Wei Yang, Mariska te Lindert, Philipp Isermann, Jan Schepens, Ralph J A Maas, Khouloud Eid, Chandrasekhar VenkataramanChandrasekhar Venkataraman, Jan Lammerding, Anotida Madzvamuse, Wiljan Hendriks, Joost te Riet, Katarina WolfDirectional 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 step-wise deformation and reshaping remain unclear. Using atomic force spectroscopy, timelapse fluorescence microscopy and shape change analysis tools, we determined 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 as 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.
Funding
Unravelling new mathematics for 3D cell migration; G1438; LEVERHULME TRUST
InCeM: Research Training Network on Integrated Component Cycling in Epithelial Cell Motility; G1546; EUROPEAN UNION
New predictive mathematical and computational models in experimental sciences; G1949; ROYAL SOCIETY; WM160017
Motility and Pattern Formation; EP/K032208/
History
Publication status
- Published
File Version
- Published version
Journal
Philosophical Transactions B: Biological SciencesISSN
0962-8436Publisher
Royal Society, TheExternal DOI
Issue
201802Volume
374Page range
1-12Department affiliated with
- Mathematics Publications
Research groups affiliated with
- Mathematics Applied to Biology Research Group Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2019-05-29First Open Access (FOA) Date
2019-05-29First Compliant Deposit (FCD) Date
2019-05-28Usage metrics
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