Changes in nuclear shape and gene expression in response to simulated microgravity are LINC complex-dependent

Microgravity is known to affect the organization of the cytoskeleton, cell and nuclear morphology and to elicit differential expression of genes associated with the cytoskeleton, focal adhesions and the extracellular matrix. Although the nucleus is mechanically connected to the cytoskeleton through the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex, the role of this group of proteins in these responses to microgravity has yet to be defined. Therefore, we used simulated microgravity achieved by growing cells on a 3d clinostat to investigate whether the LINC complex acts to mediate responses to the microgravity environment. We show that nuclear shape and differential gene expression are both responsive to simulated microgravity in a LINC-dependent manner and that this response changes with the duration of exposure to simulated microgravity. These LINC-dependent genes likely represent elements normally regulated by the mechanical forces imposed by gravity on Earth. Overall design: Response of MCF 10A engineered cells to SMG