Mechanical Characterization of the Nucleus within Live Nematodes Reveals a Step-Wise Response to Applied Forces

The nucleus is the largest and stiffest organelle in the cell. Nucleus mechanics was shown to be important for mediating the transmission of physical forces outside in and to play a role in mechanotransduction and gene regulation. Nucleus mechanics was also shown to hinder cell migration across narrow spaces associated with immune response and will cancer metastasis. Hence, there is a significant need to evaluate the viscoelastic properties of the cell nucleus mostly within a live and viable organism. Using a C. elegans model, we analyzed the physical response of the nucleus within various tissues to applied stresses. To this end, we stretched live nematodes and inspected their nuclei under an optical microscope. In contrast to the deformation dynamics of the nematode and the cells within it, the nuclei deformed non-monotonically in response to a creep measurement. Using pharmaceutical drugs of interest to manipulate the filamentous organization of the cytoskeleton and the condensation of chromatin, siRNA targeted at specific structural and linker proteins of interest and knockout lines of LINC complex genes, we developed a viscoelastic model that accounts for the abnormal physical response of the nucleus. Our work thus highlights biological mechanisms that protect the cell nucleus from physical impact due to applied forces within a live organism.