Cell mechanotransduction: cytoskeleton and related signalling pathways

Abstract

Mechanical stimuli regulate a variety of cell physiological functions including gene induction, protein synthesis, proliferation and/or differentiation; understanding mechanotransduction at the cellular level is key to understanding basic biology. Here on Earth, signal transduction affects a wide array of receptors and ligands that signal induction of gene expression. The most common signaling pathways include receptor tyrosine kinase (RTK), G-Protein coupled receptors (GPCR) and extracellular matrix components (integrins). The cytoskeleton functions to maintain cell shape and to move cellular components, separate chromosomes during mitosis and provides sensing networks for mechanotransduction. Mechanotransduction is the process of translating mechanical force on a cell into a biological response. Over the last few decades, mechanotransduction has been shown to occur via extracellular matrix, integrins, cytoskeleton signals, GTPases, adenylate cyclase, PLC and MAP kinases (MAPK), all of which play significant roles in early mechanical signaling. During the last decades a wide variety of space flight experiments have demonstrated that gravity has profound effects on whole organisms, organs and tissues, resulting for example in bone and muscle resorption as well as in the occurrence of cardiovascular malfunctioning, immuno-suppression and many other aspects of clinical medicine. Interestingly, the virtual absence of gravity also has profound effects on the cellular and molecular level, including changes in cell morphology, collapse of the actin cytoskeleton, modification of gene expression, changes in signal transduction cascades and even changes in the polymerization of tubulin. The effects of mechanical stress (e.g. gravity) or lack of stress (microgravity) on cell and molecular properties is discussed with an emphasis on the involvement of signal transduction cascades of RTK, integrins and FasR as well as their role in cytoskeleton perception of gravity in mammalian cells.