On mechanosensation, acto/myosin interaction, and hypertrophy.

Current concepts of mechanosensation are general and applicable to almost every cell type. However, striated muscle cells are distinguished by their ability to generate strong forces via actin/myosin interaction, and this process is fine-tuned for optimum contractility. This aspect, unique for actively contracting cells, may be defined as "sensing of the magnitude and dynamics of contractility," as opposed to the well-known concepts of the "perception of extracellular mechanical stimuli." The acto/myosin interaction, by producing changes in ATP, ADP, Pi, and force on a millisecond timescale, may be regarded as a novel and previously unappreciated mechanosensory mechanism. In addition, sarcomeric mechanosensory structures, such as the Z-disc, are directly linked to autophagy, survival, and cell death-related pathways. One emerging example is telethonin and its ability to interfere with p53 metabolism and hence apoptosis (mechanoptosis). In this article, we introduce contractility per se as an important mechanosensory mechanism, and we differentiate extracellular from intracellular mechanosensory effects.