Form follows function: how muscle shape is regulated by work

What determines the shape, size, and force output of cardiac and skeletal m uscle? Chicago architect Louis Sullivan (1856-1924), father of the skyscrap er, observed that "form follows function." This is as true for the structur al elements of a striated muscle cell as it is for the architectural featur es of a building. Function is a critical evolutionary determinant, not form . To survive, the animal has evolved muscles with the capacity for dynamic responses to altered functional demand. For example, work against an increa sed load leads to increased mass and cross-sectional area (hypertrophy), wh ich is directly proportional to an increased potential for force production . Thus a cell has the capacity to alter its shape as well as its volume in response to a need for altered force production. Muscle function relies pri marily on an organized assembly of contractile and other sarcomeric protein s. From analysis of homogenized cells and molecular and biochemical assays, we have learned about transcription, translation, and posttranslational pr ocesses that underlie protein synthesis but still have done little in addre ssing the important questions of shape or regional cell growth. Skeletal mu scles only grow in length as the bones grow; therefore, most studies of adu lt hypertrophy really only involve increased cross-sectional area. The hear t chamber, however, can extend in both longitudinal and transverse directio ns, and cardiac cells can grow in length and width. We know little about th e regulation of these directional processes that appear as a cell gets larg er with hypertrophy or smaller with atrophy. This review gives a brief over view of the regulation of cell shape and the composition and aggregation of contractile proteins into filaments, the sarcomere, and myofibrils. We exa mine how mechanical activity regulates the turnover and exchange of contrac tion proteins. Finally, we suggest what kinds of experiments are needed to answer these fundamental questions about the regulation of muscle cell shap e.