Unforgettable force – crosstalk and memory of mechanosensitive structures

Abstract

The ability of cells to sense and respond to mechanical stimuli is crucial for many developmental and homeostatic processes, while mechanical dysfunction of cells has been associated with numerous pathologies including muscular dystrophies, cardiovascular defects and epithelial disorders. Yet, how cells detect and process mechanical information is still largely unclear. In this review, we outline major mechanisms underlying cellular mechanotransduction and we summarize the current understanding of how cells integrate information from distinct mechanosensitive structures to mediate complex mechanoresponses. We also discuss the concept of mechanical memory and describe how cells store information on previous mechanical events for different periods of time.

From stretch to deflection: the importance of context in the activation of mammalian, mechanically activated ion channels

“…This convergence will depend on the structural elements through which the mechanical inputs are propagated and the mechanism by which these forces can lead to channel gating. The canonical view of the role of mammalian MA ion channels in mechanotransduction largely assumes that these force sensors function in the apical membrane of cells, in response to membrane stretch and deformations [2]. However, recent data on the activation and impact of MA channels in mammalian cells also suggest a role for these molecules at the cell-substrate and cellcell interfaces (Figure 2).…”

“…The conversion of a mechanical input into a biochemical signal is broadly termed mechanotransduction. Multiple mechanotransduction signalling pathways have been identified, including integrin-mediated mechanotransduction, the action of strain-gauge proteins, and coupling of the plasma membrane to the nucleus via cytoskeletal structures [2]. This review, however, will focus on mechanically activated (MA) ion Accepted Article channels, a subset of force-sensing molecules of emerging significance.…”

Cell mechanosensing underlies homeostasis of multicellular systems

“…Cells in tissues interact not only chemically but also mechanically with their surrounding environments including interstitial and vascular fluids, neighboring cells, and extracellular matrices. Extensive studies using cultured cells have successfully created a list of proteins involved in cellular mechanosensation, mechanotransduction and mechanoresponse [1,2], which provides us great opportunities to elucidate how mechanical cues and cellular responses are integrated into tissue functions including development, morphogenesis, homeostasis and pathology. As spatio-temporal information is essential for characterizing mechanical environments and dynamic behaviors of tissues, imaging and computer simulation of cellular mechanosensing/transduction/response in the 3D tissue space have great advantage to address fundamental questions on tissue functions.…”

A mechanical memory of pancreatic cancer cells

“…These complex mechanoresponses are the result of integrated signals from many distinct mechanosensitive structures such as ion channels, focal adhesions, adherens junctions, cytoskeleton, and LINC complex (6,7). Although the major mechanisms underlying cellular mechanotransduction have been clarified, the intriguing ability of cells to store information on past physical stimuli over time for future mechanical challenges remains largely unexplored (8). The long-term mechanical memory of cells is predominantly mediated by changes in gene expression through the nuclear localization of transcription factors that act as memory keep-ers for days (9)(10)(11)(12).…”