Lorijn Van der Spek

Laboratoire Matière et Systèmes Complexes MSC, UMR 7057, CNRS & Université Paris Cité

Mechanical constraint of muscle cells to promote differentiation at different scales

Abstract : The muscle is a multiscale system built up of myofibers. Myofibers differentiate from myoblasts, which differentiate from muscle stem cells. The shape of myoblasts, as well as the forces they experience, influences their differentiation. In my PhD, I have studied this phenomenon at both the single cell scale and the 3D tissue scale.

To study individual myoblasts, we place them on square or rectangular micropatterns that determine the shape of the cells. With this method, we can study the impact of shape at short timescale (3-18h post-deposit). We show that the shape of the cells influences proliferation, membrane potential and Pax7 expression.

To make samples of lab-made tissue, we use a device developed in our lab: the magnetic stretcher. By labelling myoblasts with magnetic nanoparticles, we can make them aggregate much faster into a much larger tissue than via other techniques. In a two-day span, we can form, stretch and initiate differentiation of a 500µm-thick tissue. Using this technique, we have shown that there is a collective alignment of the actin skeleton of the cells alongside the direction of stretch. We are currently investigating surface phenomena of the samples and later aim to study local differentiation in the sample. To this end, we have developed a mRNA and actin visualization technique conjugated with deep penetration microscopy to look at the emergence of differentiation patterns.