Figure 2: On the left, a simple cell stretcher using microplates in 2005 (adapted from Desprat, Biophysical Journal, 2005, 10.1529/biophysj.104.050278). On the right, a microtissue assembled on a vacuum actuated stretcher. The tissue is made of hundreds of cells and collagen. The actin is marked in green and the nuclei in blue. The scale bar is 100 µm (adapted from Walker, Scientific Report, 2020, 10.1038/s41598-020-64725-7).

A web and a magnet

To address these requirements, MICROBS team in EPFL proposed a clever design. As a substrate for the cells, they electrospun dextran fibers to form a web with mechanical properties that imitates the extracellular matrix. A paramagnetic element is glued at the center of the web and can be controlled by a matrix of magnets around the setup: rotating this matrix applies a torque on the actuator on the web, twisting it. Using a numerical clone of the web (obtained from a simple picture), the forces applied on the fibers are locally estimated. 
The magnetic actuation has a quick response time and produces forces comparable to cellular forces. As a proof of concept, the publication reports a faster and more persistent migration of fibroblasts on an actuated web exerting forces close to the one the cells would. This system can thus be used to explore the dynamical response of cells due to fibers recruitment over distances.

Figure 3: Assembly of the actuator and the web on the left (scale bar is 100 µm) and 3D view of the 3D actuation system. Adapted from Uslu, Advanced Materials, 2022, 10.1002/adma.202102641

Caption movie 1: The magnetic actuator has a response time shorter than a second that would be ideal to explore the dynamics of the cellular response when exposed to different stretches. Adapted from Uslu, Advanced Materials, 2022, 10.1002/adma.202102641

A simple yet promising tool

In the field of mechanobiology, experiments tend to become more and more elaborate and intricate, to perform the mechanical measurement in an environment as natural for the cells as possible. In contrast, this setup kept things as simple as possible, using only one actuator on a 2D web well characterized. And yet, the team did a significant step in the direction of the physiological relevance. Despite bringing a fibrillar environment for the cells, the easier to calibration than a bio extracted matrix which makes experiments more reproducible. Overall, the team of Sakar brought an elegant tool to the community, that could become a reference to better understand long range cell interactions through fibrillar environments.