Mechanical signals are critical to the development and maintenance of skeletal muscle, but the mechanisms that convert these shape changes to biochemical signals is not known. When a deformation is imposed on a muscle, changes in cellular and molecular conformations link the mechanical forces with biochemical signals, and the close integration of mechanical signals with electrical, metabolic, and hormonal signaling may disguise the aspect of the response that is specific to the mechanical forces. The mechanically induced conformational change may directly activate downstream signaling and may trigger messenger systems to activate signaling indirectly. Major effectors of mechanotransduction include the ubiquitous mitogen activated protein kinase (MAP) and phosphatidylinositol-3' kinase (PI-3K), which have well described receptor dependent cascades, but the chain of events leading from mechanical stimulation to biochemical cascade is not clear. This review will discuss the mechanics of biological deformation, loading of cellular and molecular structures, and some of the principal signaling mechanisms associated with mechanotransduction.
KeywordsSkeletal muscle; mechanotransduction; stretch
INTRODUCTIONThe detection and response to physical forces is essential to all cells, but is particularly relevant to those that play a fundamentally mechanical role. The primordial nature of the cellular interaction with the physical world suggests that its control should be highly regulated and specific, and that the response should integrate many aspects of cellular physiology. Pathways involved in detecting and producing forces in muscle overlap those involved in detecting nutrient availability (1,2), intracellular energy status (3,4), and oxidative status (5,6). The signaling pathways modulated by force, insulin and insulin-like growth factor I (IGF-I)(7), adenosine monophosphate (AMP) dependent kinase (AMPK) (8), reactive oxygen species (ROS) (9), and prostaglandins (PG) (10) seem intractably intertwined.The adaptations of skeletal muscle to mechanical signals have been widely described, and the interested reader is referred to several recent reviews (11)(12)(13)(14). The physiological increase in force generating capacity associated with activity, and the increase in flexibility associated with stretch, were recognized in antiquity, but the mechanisms by which those changes manifest are still unclear. The present intention is to consider the shape changes and forces associated with mechanical signals and juxtapose them with observed changes in biochemical signaling to determine what might contribute to the cellular perception of mechanical signals.Careful consideration of the mechanical environment is the first step to sort out that labyrinth of signaling. When one considers mechanisms by which the mechanical environment can be
NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript sensed, it is common to think of "force" and "deformation" separately. Sometimes this distinction is legitimate, bu...