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Mechanosensing in bone cells

Two-bead microrheology with whole cells. Differential interference contrast microscopy (DIC) image of a MLO-Y4 osteocyte-like cell suspended in culture medium by two optically trapped fibronectin-coated beads (diameter 4 μm). The beads are attached to opposing sides of the cell. Scale bar: 5 μm.

Specialized cells inside the bone matrix, the osteocytes, are the detectors of mechanical stress and strain and chemically signal to other cells in a complex regulatory network controlling the dynamic remodeling of bone. Understanding this regulatory system is medically important to fight age-related osteoporosis, but also for bone healing after injury, for implant surgery, dental surgery, and even to solve health problems humans encounter during space missions. We are developing methods to directly mechanically stimulate single osteocytes, to study their mechanical properties and measure their chemical signalling response, in particular the release of nitric oxide. (collaboration with J. Klein-Nulend, T. Smit, VUMC Amsterdam, Oxford)

Flow- and mechanosensing via primary cilia in kidney epithelial cells

Many cell types are mechanosensitive, which is important for communication between cells and their environment. Mechanosensitivity involves membrane channels and coupled cytoskeletal structures. Defects in mechanosensing have been linked to human diseases, such as polycystic kidney disesase (PKD). We study: (i) model systems of substrate-supported lipid membranes with embedded channels and attached polymer networks to study basic mechanical properties and channel activation, (ii) cells that sense flow, with a focus on the role of primary cilia and TRP channels. We will use optical trapping, microrheology, electrical recording and fluorescence microscopy.

Protective mechanisms and mechanosensing of vascular endothelial cells

Epithelial cancer cell (PC3) with fluorescently labeled actin, showing long protrusions embedded in a pericellular matrix (not labeled) consisting mainly of hyaluronan.

The cells lining the inside of blood vessels need to protect themselves against damage by blood flow itself and the potentially dangerous molecular contents of blood (e.g. cholesterol). It is generally believed that a highly dynamic polyelectrolyte layer on the surface of the cells, the glycocalix, is responsible for this protection and its breakdown appears to stand at the beginning of many vascular and heart diseases. Regulation of the glycocalix occurs through mechanosensing again, possibly by similar mechnisms as in the bone cells. We are studying the viscoelastic properties of the glycocalix in cultured cells and we are exploring possibilities to study the dynamic properties of this extracellular matrix inside of blood vessels. (collaboration with J. Spaan, AMC Amsterdam)