Mechanotransduction – Historical Development

Julius Wolff, a nineteenth-century anatomist, first observed that bone will adapt to the stresses it experiences and is capable of remodeling if the state of stress changes. This became known as Wolff’s Law and stands today as perhaps the earliest recognized example of the ability of living tissues to sense mechanical stress and respond by tissue remodeling (see Chapter 17 for a detailed historical review). More recently, the term “mechanotransduction” has been introduced to represent this process, often including the sensation of stress, its transduction into a biochemical signal, and the sequence of biological responses it produces. Here we use mechanotransduction in a somewhat more restricted sense, and specifically use it for the process of stress sensing itself, transducing a mechanical force into a cascade of biochemical signals.

Since Wolff’s early insight, the influence of mechanical force or stress has become increasingly recognized as one of the primary and essential factors controlling biological function. We now appreciate that the sensation of stress occurs at cellular or even subcellular scales, and that nearly every tissue and every cell type in the body is capable of sensing and responding to mechanical stimuli. Another manifestation of mechanotransduction is known as Murray’s Law [1, 2], which states that the flow rate passing through a given artery scales with the third power of its radius. This has been widely recognized to be a response of the arterial endothelium and the smooth muscle cells to remodel the arterial wall to maintain a nearly constant level of hemodynamic shear stress (at ~ 1 Pa), leading to the third power relationship. One aspect of this response is the alignment of endothelial cells in the direction of stress, first observed in studies of arterial wall morphology [4], and later vividly demonstrated in controlled in vitro experiments [5]. Other biological factors, such as soft tissue remodeling [6], changes in the thickness of the arterial wall in response to circumferential stress [7], calcification in the heart valve tissue in response to pathological solid and fluid mechanical patterns, and bone loss in microgravity [8, 9], have all been found to be influenced by mechanical stress.