New magnetic robot determines cell stiffness and traction force



Scientists have developed a small mechanical probe that can measure the inherent stiffness of cells and tissues as well as the internal forces that cells generate and influence each other. The researchers report that their new “magnetic microrobot” is the first such probe capable of quantifying both properties, and will help understand cellular processes involved in development and disease.

They detail their findings in the journal Robotics science.

Living cells generate forces through protein interactions, and these forces are very difficult to measure. Most probes can either measure forces actively generated by tissues and cells themselves, a characteristic we call traction, or they can measure their stiffness — but not both.”


Ning Wang, principal investigator, professor of mechanical sciences and engineering at the University of Illinois, Urbana-Champaign

To measure cell stiffness, researchers need a relatively rigid probe that can compress, stretch or twist tissue and determine how strong it is in resistance. But to measure internally generated contractions or expansions of cells, the probe must be relatively soft and flexible.

Like other scientists, Wang and his colleagues have already developed sensors to measure each of these traits separately. But he said he wanted to develop a more comprehensive probe that could handle both at once. Such a probe would allow a better understanding of how these properties affect diseases such as atherosclerosis or cancer, or how a fetus develops, for example.

To address this challenge, Wang and graduate student Irfan Muhagheghian searched for ways to change the mechanical properties of the probe after it was injected into the tissue of interest. They used hydrogels made of polyethylene glycol, a substance already approved for use in humans.

For the new study, the team developed a precise method for embedding a magnetic “micro cross” into a rigid PEG hydrogel. Study co-author Kristi Anseth, professor of chemical and biological engineering at the University of Colorado, Boulder, developed a method to break down and soften hydrogels using ultraviolet light.

In a series of experiments, the researchers injected their probes into 3D tumor blocks grown in the lab and into zebrafish embryos. By exposing these tissues to an electromagnetic field, the scientists activated the probes to exert various pressures on the tissue and measure tissue stiffness. Exposing the tumor mass or embryos to UV light and then softening the PEG matrix of the probes allows the probes to measure forces generated by cells within the tissue.

The probes provided accurate information about both tissue stiffness and traction, revealing for the first time that while malignant tumors may become stiffer in response to surrounding tissues, cancer cells do not change trajectories, regardless of their proximity to soft or hard materials. This challenges the popular perception that the physical properties of the underlying tissues lead to changes in the internal forces of cancer cells, allowing them to spread, Wang said.

“People believed that substrate rigidity was the driving force for cancer development,” Wang said. “Our findings do not support this claim.”

The probes also captured the pushing and pulling of cells during embryonic development, Wang said, which could provide new insights into how these oscillations fit the pattern of organs, tissues and limbs as animals develop from single cells to complex tissues. The embryonic work was conducted by researchers at the Chinese Academy of Sciences and Huazhong University of Science and Technology in Wuhan, China.

“We believe that the large force oscillations detected in embryos are very important in driving the early stages of development,” Wang said.

Wang is also a professor of bioengineering and a member of the Carle Illinois University College of Medicine, the Beckman Institute for Advanced Science and Technology, and the Carl R.

The National Institutes of Health, the National Science Foundation, and the National Natural Science Foundation of China supported this research.

Source:

Journal reference:

Mohaghegian, E.; et al. (2023) Measuring the stiffness and strengths of tumor colonies and embryos using a magnetic robot. Robotics science. doi.org/10.1126/scirobotics.adc9800.



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