We composed this image to show that muscles are not just motors; they are also sensors. The worm on the cover of the December 16 issue of Biophysical Journal is an adult Caenorhabditis elegans imaged on a Leica SP8 confocal microscope. We fixed the animal and stained F actin with fluorescent phalloidin and the cell membranes with wheat germ agglutinin. We then collected a z stack that we deconvolved and collapsed into a maximum projection. The yellow signal is F actin in the sarcomeres of the striated body wall muscles running along the sides of the worm and in the radially arranged filaments of the terminal bulb of the pharynx, which forms the bright ring near the center of the image. The cyan outlines are cell membranes, which trace the body and the edges of each myocyte. The purple signal is PEZO-1, an endogenously tagged mechanosensitive channel that we found both in the hypodermis and at the sarcolemma of body wall muscles.
In other words, yellow shows the machinery that makes force, cyan shows the walls of the cells that contain it, and purple shows the sensors embedded in those walls. We usually think of muscles as followers that simply obey whatever pattern of activity the nervous system sends to them. In this work, we show that muscles in C. elegans are also listening to the forces they generate. PEZO-1 sits in very specific positions on the muscle membrane, where stretching and compression occur, and shapes how calcium flows during contraction.
Our lab works at the edge of the self, at the interface between the organism and the world it inhabits. We are interested in how physical forces, both external and internal, constrain, shape, and enable behavior. This image exemplifies that interaction. The yellow fibers belong to the cellular machinery that generates mechanical force, the cyan membranes outline the boundary between these cells and their environment, and the purple tag labels the PEZO-1 proteins that monitor this physical dialogue between cell and world, not just passively tallying forces but shaping the behavior and output of these muscles so they can meet the ever-changing demands they face.
Even though this is a tiny worm, the questions are very familiar in real life. When a child with muscular dystrophy learns to walk, or when any of us train, decondition, or recover from injury, muscles need to sense how hard they are working and adapt to changing loads. In the paper, we show that PEZO-1 in a single tail muscle, vm21, is linked to the expression of dystrophin, the protein missing in Duchenne muscular dystrophy. That suggests that the same mechanosensitive feedback that helps a worm swim efficiently may also communicate with structural proteins that protect muscles under strain. The picture on the cover turns that abstract feedback loop into something one can see.
For readers who do not work in our field, one way to look at this image is as a map of feedback in a living tissue. The yellow filaments are the engines, the cyan lines are the walls of the engine room, and the purple puncta are the strain gauges, which tell the system when the load has changed. Our hope is that, by understanding how a simple animal like C. elegans uses channels like PEZO-1 to fine-tune movement in water and on land, we will be better prepared to ask the right questions about human muscle performance and disease.
You can find more about this work and related projects on our lab website at https://about.illinoisstate.edu/avidal/ or our YouTube channel at https://www.youtube.com/@vidal-gadeac.eleganslab4632.
— Adina Fazyl, Mackenzie Jones, Damiano Marchiafava, Shifat Niha, Erin Sawilchik, Wolfgang Stein, and Andrés Vidal-Gadea