Muscle mechanobiology: Muscles, Chromatin and the forces that connect them

Speaker Dr Dana Lorber, Department of Molecular Genetics, Weizmann Institute of Science, Israel

Title Muscle mechanobiology:Muscles, Chromatin and the forces that connect them

Host Yaniv Hinits

 

Abstract Mechanotransduction pathways have been identified as major regulators of cell activity in various cell types, but little is known about these processes in muscle cells, even though it is an archetypical force generating tissue. Studying muscle and myonuclei dynamics at the molecular and tissue level yielded many research methods, yet some have drifted away from the in vivo environment. We developed a device that enables the studying of active muscles in their native environment. This device allows live imaging of myonuclei, muscle structures, and organelles that have been genetically tagged with fluorescent markers in intact Drosophila larva and the quantification of their spatiotemporal dynamics under various conditions. This new approach has enabled our lab to explore questions that could not be previously addressed. We found that the mechanical dynamics of myonuclei during muscle contraction was synchronized along the muscle and correlated with uniform genetic activity of the nuclei along the fiber. We also found that larvae with mutations in the LINC complex lack this mechanical and biological uniformity, which results in impaired locomotion. Using a similar methodology, we studied chromatin organization in myonuclei. We found that chromatin, both active and repressed, organizes at the periphery of the nucleus, leaving a chromatin devoid volume at the center of the nucleus. We found this peripheral organization also in human cells, suggesting that it is evolutionarily conserved. Taken together, these results show the potential of studying muscle mechanobiology in live intact models and the necessity to study both muscle and myonuclei organization and dynamics to gain insights into mechanotransduction processes.