Physical limits of cell migration: Control by ECM space and nuclear deformation and tuning by proteolysis and traction force
| Autor: | Amanda L. Willis, Katarina Wolf, Mariska te Lindert, Stephen J. Weiss, Robert M. Hoffman, Carl G. Figdor, Peter Friedl, Marina Krause, Joost te Riet, Stephanie Alexander |
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| Rok vydání: | 2013 |
| Předmět: |
Integrins
Surface Properties Integrin Matrix metalloproteinase Interstitial cell Cell Line Extracellular matrix 03 medical and health sciences 0302 clinical medicine Immune Regulation [NCMLS 2] Cell Movement medicine Animals Humans Cytoskeleton 030304 developmental biology Membrane transport and intracellular motility Translational research [NCMLS 5] 0303 health sciences biology Proteolytic enzymes Translational research Immune Regulation [ONCOL 3] Cell migration Hydrogels Cell Biology Anatomy Matrix Metalloproteinases Extracellular Matrix Rats Kinetics medicine.anatomical_structure 030220 oncology & carcinogenesis Proteolysis biology.protein Biophysics Cattle Collagen Nucleus |
| Zdroj: | Journal of Cell Biology, 201, 7, pp. 1069-84 Journal of Cell Biology, 201, 1069-84 |
| ISSN: | 0021-9525 |
| DOI: | 10.1083/jcb.201210152 |
| Popis: | Item does not contain fulltext 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 microm(2); T cells, 4 microm(2); neutrophils, 2 microm(2)). 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. |
| Databáze: | OpenAIRE |
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