Instructing myofibrillogenesis in human muscle by forces and shapes
Presentation of the hosting teams
The Schnorrer lab pioneers the interface between developmental and cell biology with biophysics in order to understand how the ordered sarcomeric machine is assembled in Drosophila and human muscle models.
The Theodoly lab develops microfluidic and micropatterning tools to generate defined environments. These enable to quantitatively study the mechanical interaction of cells with their environment.
Skeletal muscle fibers are large multinucleated cells, which mechanically connect two skeletal elements. The contractile forces are generated by highly regular mini-machines called sarcomeres, which are organized in long periodic chains called myofibrils. How can such long and regular myofibrils form during development? Using the fly model, the Schnorrer lab developed the tension-driven self-organization hypothesis of myofibrillogenesis, which suggests that mechanical tension acts as a compass to coordinate the assembly of many sarcomeres into long myofibrils. This hypothesis needs to be tested in human muscle.
We aim to generate human muscle fibers of defined sizes and shapes by 2D- or 3D-micropatterning and quantify the assembly and regularity of the sarcomeric pattern (Aim1). We then want to directly manipulate the forces by using stretchable PDMS-derived substrates and observe the impact on myofibrillogenesis (Aim2). Finally, we will directly quantify the forces generated by the differentiating muscle fibers by monitoring the deformation of the substrate with embedded beads (Aim3).
In this inter-disciplinary PhD-project we take advantage of the extensive knowledge of the Theodoly lab in generation of micropatterned surfaces to directly quantify and manipulate forces and shapes of developing human muscle fibers in culture. We will use human induced pluripotent stem cells to generate a pure myoblast population that can be differentiated into millimeter long muscle fibers. This approach will directly test how defined forces and shapes instruct myofibrillogenesis in human muscle, and will thus generalize the tension-driven myofibril self-organization model to humans.
PhD student’s expected profile
The curiosity driven PhD student should have a firm biological or biophysical education and enjoy to work at the interface between biology and biophysics. Experience in quantitative imaging, image analysis or bioengineering is a plus.