Today there is a big interest in muscle related disorders, such as sarcopenia, the age-related decline in muscle mass that will inflict us all-if it hasn’t already… As a result, viable methods for combating muscle wasting disorders are urgently being sought. But in order to achieve satisfactory results new therapies and technologies to enhance muscle regeneration have to be developed based on a better understanding of the exact processes occurring at the transition points, cell division (proliferation) and cell fusion (differentiation), of the different stages in muscle development. Activated myoblasts first undergo many rounds of cell division. Depending on the needs of the cells, myoblasts may next withdraw from the cell cycle to fuse to form myotubes. Division and fusion are differentially modulated by mechanical stimuli transmitted to the cell’s biosynthetic mechanisms via the actin-based cytoskeleton; specifically cyclic stretch promotes proliferation and inhibits fusion.
The best way to unravel the delicate interdependency of proliferation and differentiation is to understand how environmental signals are communicated from the extracellular matrix via the cytoskeleton and ultimately transduced into a biochemical response arising from the activation of enzymes (short term) as well as the transcription of genes (long term). Moreover, calcium appears to be an important instigator of cellular responses in both the short- and long-terms.
The platform of choice for assessing cell response to mechanical stimuli is the STREX mechanical cell strain instrument from B-Bridge international, inc. A mechanical engine provides reliable long and short term uniaxial stretch of an elastic substrate. The substrates which are made of PDMS in our lab can be functionalized with a protein of choice either by covering the entire surface or as a pattern. We have preliminary results of up and down regulation of different gene expressions under certain stretching and chemical conditions indicating that the activation of stretch activated calcium channels is linked to myogenic behaviour.
Microscopic changes during myogenesis add another angle to the unravelling of cell response at the transition points. To view a project where we have used atomic force microscopy in combination with confocal laser scanning microscopy to image submicrometer features on behaving myoblasts, click here.
This project was carried out under the auspices of the Mechanobiology group of the LBB.
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