The athletes among us know it well: when you subject your body to mechanical forces, your muscles grow and your bones get stronger. Movement scientists describe the impact of these forces at the body level, but a lot happens at the cellular level as well. And that is what PhD candidate Roel Kooi focuses on. Four years ago, he left Wageningen for a challenging PhD track at TU/e in the Microsystems research group. There, he worked on directing bone cells using magnetic cilia. “Mechanical forces cause cells to send all kinds of signals and change their behavior. That’s ultimately what allows your muscles and bones to grow.”

Mechanical stress isn’t just important for growing cells – it’s essential for any cell to function properly, Kooi emphasizes. “You can see this very clearly in the bodies of bedridden patients, where a lot changes at the cellular level due to lack of movement. Or in astronauts who spend long periods of time in outer space, where their cells are no longer exposed to gravity. Their hearts pump less forcefully, and their other muscles also gradually atrophy. It’s a downward spiral.”

Replacing diseased kidney cells

In recent years, we’ve gained more and more insight into what forces affect cells in the body and how. But replicating them, that’s a different story. Still, it’s important, Kooi explains. “Of course, you want cells to grow in the most realistic way possible when you’re using them in your research. Mechanical stress causes cells to produce different proteins and behave differently as a result. And that, in turn, causes them to send out different signal substances to their surroundings.”

In addition, Kooi and his colleagues want to explore how to influence cell behavior itself. “For example, when you’re trying to stimulate a tissue to repair itself. Or if you want to direct the differentiation of stem cells into specific types of body cells, such as bone, cardiac muscle or kidney cells. For these kinds of biomedical applications, we’re looking for a method that allows us to control cells as precisely as possible.”

In Professor Jaap den Toonder’s research group, many experiments are conducted with magnetic “cilia”. With these tiny artificial vibrating hairs, Den Toonder developed a new technology to control forces and flows in mini-labs, such as an Organ-on-a-Chip. Until now, it had not been possible to grow cells on a substrate of magnetic cilia and stimulate them mechanically. And it proved to be quite a challenge, Kooi says with a laugh.

Cilia forest

“The cilia are made from a flexible magnetic polymer. We can create pillars that are 6 micrometers long and 400 nanometers in diameter, but the most commonly used ones are 23 micrometers in length and 2 micrometers in diameter. That’s about 30 times thinner than a human hair, which makes them well-proportioned for our cultured cells. The pillars shouldn’t be too large, because we want the cells to grow between the cilia, not on top of them. And the density must be right too; otherwise, it turns into a chaotic cilia forest.”

This platform, along with an electromagnet, formed the basis for a new setup Kooi developed. “In this lab system – NanoMAC (Nano Magnetic Artificial Cilia) – we can now control the cilia with extreme precision. How fast they move, with how much force, and for how long.”

The cells turned out to grow well on the polymer substrate – a promising result. But to his frustration, Kooi found that, with the cells included in the setup, the cilia stopped moving altogether. “That cost quite a bit of time and head-scratching. Eventually, we figured out it was due to the fluid environment. We could control the cilia’s movement very precisely in ethanol, but cells need an aqueous environment. And that proved detrimental to the cilia’s mobility.”