Informatics-based analysis of mechanosignaling in the laminopathies

The A- and B-type lamins are the primary building blocks of the lamina-a proteinaceous meshwork underlying the nuclear envelope (NE). In the last decade, some 25 diseases have been linked to mutations in genes encoding proteins of the NE and lamina, with about half being caused by mutations in the Lamin A gene. Cells, either from patients or from mice carrying lamin mutations, frequently exhibit deformed nuclei accompanied by compromised mechanical properties in both the nucleus and the cytoplasm, implying that defects in the mechanical integrity of the nuclei and in mechanosignaling contribute to the pathology of these diseases. We describe a procedure to study total gene expression of mutant cells subjected to uniaxial mechanical strain by culturing them on a deformable surface. Using our procedure, enough high-quality RNA can be collected from these samples for microarray and informatics analysis. Such analysis may provide valuable information regarding the changes in gene expression and signaling pathways that may underlie the pathologies of the various diseases, which in turn may arise as a consequence of defective responses to mechanical strain.