Mohammad R.K. Mofrad: Cellular Mechanosensing: Signal Transduction Pathways from Extracellular Microenvironment to the Nucleus

abstract:

It is now widely established that living cells sense mechanical signals, and respond actively by changing their phenotype. Cellular mechanotransduction is mediated by a combination of biochemical and biophysical mechanisms via mechanically induced changes in the structure and function of specific molecules and molecular complexes. Our specific attention is on the role of three macromolecular systems in cellular mechanotransduction, namely the integrin-mediated focal adhesions bridging the cell with the extracellular matrix (ECM), and linkers of the nucleoskeleton and cytoskeleton (LINC complexes), and the nuclear pore complex (NPC) at the interface between the cytoplasm and nucleus. Focal adhesions are the immediate sites of cell interaction with the ECM, and as such they play a key role in mechanosensing and mechanotransduction at the edge of the cell. LINC complexes physically link the cytoskeleton and nucleoskeleton to regulate force transmission to the nucleus; their direct associations with focal adhesions through filamentous actin bundles results in ultrafast mechanotransduction. Nuclear pores could also play a role in the overall process of cellular mechanotransduction by exquisitely controlling the material transport in and out of the nucleus, thereby regulating gene expression and protein synthesis. In this talk, I will present some of our recent efforts aimed at better understanding of these interconnected molecular systems in the context of cellular mechanotransduction.