Objective Biological cells possess a chemical “sense of smell” and a physical “sense of touch”. Structure, dynamics, development, differentiation and even apoptosis of cells are guided by physical stimuli feeding into a regulatory network integrating biochemical and mechanical signals. Cells are equipped with both, force-generating structures, and stress sensors including force-sensitive structural proteins or mechanosensitive ion channels. Pathways from force sensing to structural and transcriptional controls are not yet understood.The goal of the proposed interdisciplinary project is to quantitatively establish such pathways, connecting the statistical physics and the mechanics to the biochemistry. We will measure and model the complex non-equilibrium mechanical structures in cells, and we will study how external and cell-generated forces activate sensory processes that (i) act (back) on the morphology of the cell structures, and (ii) lead to cell-fate decisions, such as differentiation. The most prominent stress-bearing and -generating structures in cells are actin/myosin based, and the most prominent mechanoactive and -sensitive cell types are fibroblasts in connective tissue and myocytes in muscle. We will first focus on actin/myosin bundles in fibroblasts and in sarcomeres in developing heart muscle cells. We will observe cells under the influence of exactly controlled external stresses. Forces on suspended single cells or cell clusters will be exerted by laser trapping and sensitively detected by laser interferometry. We furthermore will monitor mechanically triggered transcriptional regulation by detecting mRNA in the nucleus of mouse stem cells differentiating to cardiomyocytes. We will develop fluorescent mRNA sensors that can be imaged in cells, based on near-IR fluorescent single-walled carbon nanotubes.Understanding mechanical cell regulation has far-ranging relevance for fundamental cell biophysics, developmental biology and for human health. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesdevelopmental biologyengineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensorsnatural sciencesbiological sciencesbiophysicsnatural sciencesphysical sciencesopticslaser physics Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-PE3 - ERC Advanced Grant - Condensed matter physics Call for proposal ERC-2013-ADG See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution GEORG-AUGUST-UNIVERSITAT GOTTINGEN STIFTUNG OFFENTLICHEN RECHTS EU contribution € 2 425 200,00 Address WILHELMSPLATZ 1 37073 Gottingen Germany See on map Region Niedersachsen Braunschweig Göttingen Activity type Higher or Secondary Education Establishments Principal investigator Christoph Friedrich Schmidt (Prof.) Administrative Contact Nadja Daghbouche (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all GEORG-AUGUST-UNIVERSITAT GOTTINGEN STIFTUNG OFFENTLICHEN RECHTS Germany EU contribution € 2 425 200,00 Address WILHELMSPLATZ 1 37073 Gottingen See on map Region Niedersachsen Braunschweig Göttingen Activity type Higher or Secondary Education Establishments Principal investigator Christoph Friedrich Schmidt (Prof.) Administrative Contact Nadja Daghbouche (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
