Physical limits of cell migration: Control by ECM space and nuclear deformation and tuning by proteolysis and traction force
Katarina Wolf,Mariska te Lindert,Marina Krause,Stephanie Alexander,Joost te Riet,Amanda L. Willis,Robert M. Hoffman,Carl G. Figdor,Stephen J. Weiss,Peter Friedl +9 more
TLDR
The physical limits of cell migration in dense porous environments are dependent upon the available space and the deformability of the nucleus and are modulated by matrix metalloproteinases, integrins and actomyosin function.Abstract:
Cell migration through 3D tissue depends on a physicochemical balance between cell deformability and physical tissue constraints. Migration rates are further governed by the capacity to degrade ECM by proteolytic enzymes, particularly matrix metalloproteinases (MMPs), and integrin- and actomyosin-mediated mechanocoupling. Yet, how these parameters cooperate when space is confined remains unclear. Using MMP-degradable collagen lattices or nondegradable substrates of varying porosity, we quantitatively identify the limits of cell migration by physical arrest. MMP-independent migration declined as linear function of pore size and with deformation of the nucleus, with arrest reached at 10% of the nuclear cross section (tumor cells, 7 µm2; T cells, 4 µm2; neutrophils, 2 µm2). Residual migration under space restriction strongly depended upon MMP-dependent ECM cleavage by enlarging matrix pore diameters, and integrin- and actomyosin-dependent force generation, which jointly propelled the nucleus. The limits of interstitial cell migration thus depend upon scaffold porosity and deformation of the nucleus, with pericellular collagenolysis and mechanocoupling as modulators.read more
Citations
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Nuclear envelope rupture and repair during cancer cell migration
Celine Denais,Rachel M. Gilbert,Philipp Isermann,Alexandra L. McGregor,Mariska te Lindert,Bettina Weigelin,Patricia M. Davidson,Peter Friedl,Peter Friedl,Katarina Wolf,Jan Lammerding +10 more
TL;DR: Investigation of mammalian tumor cell migration in confining microenvironments in vitro and in vivo indicates that cell migration incurs substantial physical stress on the NE and its content and requires efficient NE and DNA damage repair for cell survival.
Journal ArticleDOI
Effects of extracellular matrix viscoelasticity on cellular behaviour.
TL;DR: The role of viscoelasticity of tissues and extracellular matrices in cell–matrix interactions and mechanotransduction and the potential utility of vis coelastic biomaterials in regenerative medicine are explored.
Journal ArticleDOI
Concepts of extracellular matrix remodelling in tumour progression and metastasis
TL;DR: This review focuses on how tumour and tumour-associated stromal cells deposit, biochemically and biophysically modify, and degrade tumours' extracellular matrix (ECM).
Journal ArticleDOI
ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death
Matthew Raab,Matteo Gentili,H de Belly,Hawa Racine Thiam,Pablo Vargas,A J Jimenez,F Lautenschlaeger,Raphaël Voituriez,Ana-Maria Lennon-Duménil,Nicolas Manel,Matthieu Piel +10 more
TL;DR: Nuclear envelope opening in migrating leukocytes could have potentially important consequences for normal and pathological immune responses and survival of cells migrating through confining environments depended on efficient nuclear envelope and DNA repair machineries.
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Modes of cancer cell invasion and the role of the microenvironment
TL;DR: Future studies will clarify how the combination of stromal network structure, tumor cell signaling and extracellular signaling cues influence cancer cell migration and metastasis.
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