CHAMPAIGN, Ill. – Scientists have created a small testing machine that can measure the stiffness of tissues and cells as well as the internal forces that cells produce and act on each other. Their new magnetic microrobot is the first such test to be able to measure both properties, the researchers report, and will help understand cellular processes related to development and disease.
They detail their findings in the journal Science Robotics.
“Living cells produce energy through the interaction of proteins, and it is very difficult to measure this energy,” said Ning Wang, a professor of mechanical science and engineering at the University of Illinois Urbana-Champaign who led the research. “Most probes can measure the force produced by cells and the cells themselves, which is a characteristic we call traction, or they can measure their weight – but not both.”
To measure tissue stiffness, researchers need a relatively stable probe that can compress, stretch or twist the tissue and measure how strongly it resists. But to measure the contraction or expansion of the cells themselves, the testing machine must be simple and easy.
Like other scientists, Wang and his colleagues had already conducted research to measure each of these qualities individually. But he said he wants to create a comprehensive study that can deal with them at the same time. Such an analysis can give you a better understanding of how these properties affect diseases such as arteriosclerosis or cancer, or how the embryo develops, for example.
To address this challenge, Wang and graduate student Erfan Mohagheghian looked for ways to change the properties of the probe after inserting it into the cells of interest. They used hydrogels made from polyethylene glycol, a material not yet approved for use in humans.
For the new study, the team developed a precise method for inserting a magnetic microcross into a rigid PEG hydrogel. Co-author Kristi Anseth, a professor of chemical and biological engineering at the University of Colorado, Boulder, had already developed a method to degrade and soften the hydrogel using ultraviolet light.
In a series of experiments, the researchers inserted their probes into 3D tumor masses and into zebrafish eggs. By placing these cells in an electrical field, the scientists activated probes to apply different pressures to the cells and measure the stiffness of the cells. Exposing a tumor mass or embryo to UV light softens the PEG matrix of the probes, allowing the probes to measure the energy produced by the cells inside the cells.
The probes provided precise information about cell stiffness and adhesion, revealing for the first time that while malignant tumors may be stiff in response to adjacent cells, cancer cells do not change connections of them, regardless of proximity to soft or hard materials. Wang says that this challenges the common belief that the physical properties of cancer cells change in the internal dynamics of cancer cells, which allows them to metastasize.
“People used to think that the stiffness of the substrate was the driving force behind cancer progression,” Wang said. “Our results do not support this.”
The probes also captured the push and pull of cells during embryonic development, which could provide new insight into how such oscillations coordinate the formation of organs, tissues and limbs. as animals evolve from single cells to complex cells, Wang said. The embryonic work was carried out by researchers from the Chinese Academy of Sciences and Huazhong University of Science and Technology in Wuhan, China.
“We believe that the large-scale oscillations detected in embryos are very important in driving the early stages of development,” said Wang.
Wang is also a professor of bioengineering and a member of the Carle Illinois College of Medicine, the Beckman Institute for Advanced Science and Technology and the Carl R. Woese Institute for Genomic Biology at the U. of I.
The National Institutes of Health, the National Science Foundation and the National Natural Science Foundation of China supported this research.