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COMMENTARY
HIGHLIGHTED TOPICS
Biomechanics and Mechanotransduction in Cells and Tissues
Mechanical stimuli play key roles in the regulation of genes that determine skeletal muscle fiber phenotype and increase in muscle mass. Accordingly, muscle mass and phenotypic composition can be dramatically altered by functional demands imposed during developmental growth, exercise, aging, and disease. Determining the molecular networks that regulate muscle fiber hypertrophy and phenotype and defining the nature of the links between mechanical signals and gene activation and repression are crucial to a fundamental understanding of muscle function in health and disease. In the first featured article, entitled "Expression of Ankrd2 in fast and slow muscles and its response to stretch are consistent with a role in slow muscle function," Dr. G. Mckoy and colleagues (2) explored the role of Ankrd2 gene in slow muscle adaptation. Passive stretch of skeletal muscle stimulates muscle growth and enhances expression of slow muscle genes, allowing the muscle to adjust to its new functional length and economize its use of ATP. The molecular pathways underlying this adaptive response are complex and rely on induction and differential expression of genes that influence both hypertrophy and fast-to-slow muscle transition. In search of regulatory genes involved in this process, these investigators identified Ankrd2 as a stretch response gene upregulated during passive stretch-induced muscle adaptation. Expression of Ankrd2 was greater in slow muscles than in fast and declined during denervation, coinciding with slow-to-fast fiber transition in denervated muscle. In kyphoscoliotic mice lacking hypertrophic response to functional overload, the slower muscle phenotype corresponded with elevated Ankrd2 expression. These observations indicate that Ankrd2 is a stretch-responsive gene associated with slow muscle adaptation. Furthermore, the ability of Ankrd2 to interact with titin, a stretch-sensitive protein, suggests a possible functional link between differential gene expression and sensing mechanical stretch via titin. Future studies will be necessary to test this hypothesis and deepen our understanding of how sensing mechanical signals lead to changes in gene expression and, hence, phenotypic adaptation in muscle.
Mechanical stimuli can also interact with electrophysiological properties of cells and tissues. In the second featured article, entitled "Mechanoelectrical excitation by fluid jets in monolayers of cultured cardiac myocytes" Dr. C.-R. Kong and colleagues (1) addressed potentially adverse effects of mechanical forces that may cause spurious excitation of cardiac tissue and, possibly, sustained arrhythmia. Mechanotransduction in the heart has been investigated largely within the context of mechanoelectric feedback (MEF), a well-studied phenomenon that links electrophysiological changes in heart cells and tissue to stretch. These investigators took a novel approach to studying MEF by applying brief, microscopic fluid jets to flat monolayers of cultured cardiac cells and monitoring the electrical activity of the cells using optical mapping and voltage-sensitive dyes. The jets produced regions of pressure and shear stress within the monolayer, causing the monolayer to excite in a random fashion. This study is the first to show that cardiac cells electrically respond, at a tissue level, to mechanical forces other than stretch. In fact, cardiac cells respond to pressure and shear stress, two forms of mechanical force also at work in the beating heart. These investigators found that pulsatile fluid jets can trigger propagating action potentials and, in rare instances, reentrant arrhythmia. This novel use of cardiac cell monolayers may lend further insight into MEF. The monolayer, comprised of hundreds of thousands of cells, reflects the large-scale, tissue-level electrophysiological function and behavior not present in individual cells. At the same time, the cell monolayer may be manipulated on a cellular scale by using patterning techniques to determine the possible roles of tissue architecture and cell geometry in mechanoelectrical functioning of the cell network. Finally, the monolayer provides a vehicle by which to study the influence of the biochemical and physical environment of cardiac cells, as well as interactions between cardiac and noncardiac cell types in the heart.
Journal of Applied Physiology
June 2005, Volume 98
REFERENCES
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