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.