A5006268986- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- Protease and Inhibitor Mechanisms
- Microtubule and mitosis dynamics
- 3D Printing in Biomedical Research
- Nuclear Structure and Function
- Ruminant Nutrition and Digestive Physiology
- Reproductive Physiology in Livestock
- Cancer Cells and Metastasis
- RNA Research and Splicing
- Peptidase Inhibition and Analysis
- Ion Transport and Channel Regulation
- Bone Tissue Engineering Materials
- Collagen: Extraction and Characterization
- Planarian Biology and Electrostimulation
- Muscle metabolism and nutrition
- Cancer-related Molecular Pathways
- Virus-based gene therapy research
- Magnetic and Electromagnetic Effects
- Advanced Fluorescence Microscopy Techniques
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Barrier Structure and Function Studies
- Proteoglycans and glycosaminoglycans research
- Animal health and immunology
- Cell Image Analysis Techniques
Radboud University Medical Center
2013-2023
Radboud University Nijmegen
2013-2023
University Medical Center
2015-2023
Radboud Institute for Molecular Life Sciences
2014-2023
Google (United States)
2019
Freie Universität Berlin
2001-2013
Polytechnic University of Turin
2012
Deutsche Forschungsgemeinschaft
2008
University of Würzburg
1999-2007
GTx (United States)
2004
Invasive tumor dissemination in vitro and vivo involves the proteolytic degradation of ECM barriers. This process, however, is only incompletely attenuated by protease inhibitor–based treatment, suggesting existence migratory compensation strategies. In three-dimensional collagen matrices, spindle-shaped proteolytically potent HT-1080 fibrosarcoma MDA-MB-231 carcinoma cells exhibited a constitutive mesenchymal-type movement including coclustering β1 integrins MT1–matrix metalloproteinase...
Cell migration through 3D tissue depends on a physicochemical balance between cell deformability and physical constraints. Migration rates are further governed by the capacity to degrade ECM proteolytic enzymes, particularly matrix metalloproteinases (MMPs), integrin- 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...
Repairing tears in the nuclear envelope The segregates genomic DNA from cytoplasm and regulates protein trafficking between cytosol nucleus. Maintaining integrity during interphase is considered crucial. However, Raab et al. Denais show that migrating immune cancer cells experience frequent transitory ruptures when they move through tight spaces (see Perspective by Burke). reseals rapidly interphase, assisted components of ESCRT III membrane-remodeling machinery. Science , this issue pp. 359...
The cell nucleus is the largest and stiffest organelle rendering it limiting compartment during migration of invasive tumor cells through dense connective tissue. We here describe a combined atomic force microscopy (AFM)–confocal approach for measurement bulk nuclear stiffness together with simultaneous visualization cantilever–nucleus contact fate cell. Using cantilevers functionalized either tips or beads spring constants ranging from 0.06–10 N m−1, force–deformation curves were generated...
Cell migration on and through extracellular matrix is fundamental in a wide variety of physiological pathological phenomena, exploited scaffold-based tissue engineering. Migration regulated by number matrix- or cell-derived biophysical parameters, such as fiber orientation, pore size, elasticity, cell deformation, proteolysis, adhesion. We here present an extended Cellular Potts Model (CPM) able to qualitatively quantitatively describe efficiencies phenotypes both two-dimensional substrates...
Metastatic cancer cells differ from their non-metastatic counterparts not only in terms of molecular composition and genetics, but also by the very strategy they employ for locomotion. Here, we analyzed large-scale statistics migrating on linear microtracks to show that metastatic follow a qualitatively different movement than non-invasive counterparts. The trajectories display clusters small steps are interspersed with long "flights". Such movements characterized heavy-tailed, truncated...
The balanced activity of microtubule-stabilizing and -destabilizing proteins determines the extent microtubule dynamics, which is implicated in many cellular processes, including adhesion, migration, morphology. Among destabilizing proteins, stathmin overexpressed different human malignancies has been recently linked to regulation cell motility. observation that was recurrent metastatic sarcomas prompted us investigate contribution tumor local invasiveness distant dissemination. We found...
Multiphoton microscopy has become a standard method for noninvasive imaging of thick specimens with subcellular resolution. Higher harmonic generation (HHGM), based on nonlinear multiphoton excitation, is contrast mechanism the structural and molecular native samples in cell culture fixed live tissues, both, three-dimensional four-dimensional reconstructions. HHGM comprises second third (SHG, THG) ordered molecules, can be obtained without exogenous labels, provides detailed real-time...
Directional cell migration in dense three-dimensional (3D) environments critically depends upon shape adaptation and is impeded depending on the size rigidity of nucleus. Accordingly, nucleus primarily understood as a physical obstacle; however, its pro-migratory functions by stepwise deformation reshaping remain unclear. Using atomic force spectroscopy, time-lapse fluorescence microscopy change analysis tools, we determined nuclear size, deformability, morphology HT1080 fibrosarcoma cells...