NSF/MCB-BSF: DYNAMIC MEASUREMENTS OF NUCLEAR MECHANOTRANSDUCTION IN SKELETAL MUSCLE CELLS IN VITRO AND IN VIVO

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Cells in an organism respond to mechanical forces, enabling the cells to adapt to their physical environment. This "mechanotransduction" process, in which mechanical stimuli is translated into biochemical signals that control cellular functions, is particularly relevant in muscle tissue: when exercised, muscle increases in size (hypertrophy), while lack of activity results in progressive muscle loss (atrophy). The underlying mechanism by which muscle cells "sense" the mechanical input remains unclear. This project examines the hypothesis that the nucleus, which houses the cell's genomic information, serves as a cellular mechanosensor. The diverse and multidisciplinary research in this project provides an outstanding training environment for biology and engineering students alike. The Lammerding lab will host and mentor high-school and Cornell pre-freshmen students, particularly underrepresented minority and first-generation college students, as part of newly created outreach modules. The work will involve the development of advanced high resolution imaging approaches in combination with genetic and mechanical perturbation of subcellular mechanics. This project will provide measurements of the forces acting on the nucleus during muscle contraction and of the induced deformation of the cell nucleus. Coupled with an analyses of the induced changes in genome organization and gene expression, the research will answer if/how force-induced deformation of the nuclei in muscle cells can induce adaptive responses in gene expression. Insights gained from this project are not only critical for understanding how muscles adapt to mechanical stimuli, but will also provide clues into how other cells, such as those in bones or blood vessels, respond to their dynamic mechanical environments. This research was funded by a joint Israeli and United States program in which the NSF provides funding for the US laboratory, located at Cornell University in New York, while the US-Israel Binational Science Foundation (BSF)in Israel provides funds for the collaborating Israeli lab at the Weizmann Institute of Science in Rehovot.