Nearly 30% of breast cancer metastasizes (spreads) to other organs, with bones being among the most frequent sites. Seeking to better understand how this happens, a team of researchers at the School of Science at Indiana University – Purdue University Indianapolis (IUPUI; Indianapolis, IN) used a fluorescence method to study the mechanics of cell migration, which can possibly explain how cancer cells generate enough force to move from the primary tumor site through the body and then settle into bones, says Jing Liu, an assistant professor in the school's Department of Physics, a Purdue University program and a co-corresponding author of the paper that describes the work.
"From a physics point of view, all the cell migration is driven by force," Liu says. "We really want to discover the force architecture of a cell and deliver the biomechanical and biophysical explanations toward cellular activities. The major focus of our lab is developing imaging methods to physically interpret cancer biology."
"We are working with mathematicians and engineers to develop a mathematical model and physical model of the cell migration," Liu says.
A tension sensor based on Förster resonance energy transfer (FRET; also referred to as fluorescence resonance energy transfer) was used to monitor the force dynamics during cell movement. The sensor, equipped with FRET molecules, acts like a spring to measure the tiny amount of force that is generated by the cancer cell through focal adhesion and that drives the cell to move. As the cancer cell moves, the spring expands—researchers measure the force by monitoring the change of FRET interactions.
The research team monitored the mobility of the cancer cells and found that when a cancer cell interacts with and gets very close to a bone cell, it exhibits low tensions and slow mobility, Liu says. The researchers hope this finding might lead to clues for how to control—and eventually stop—cell migration.
"This gives us a more precise measurement of how fast the cell is moving and where the cell will go to," Liu says. It will also provide feedback to cancer biologists, showing the impact of a drug or other treatment on the movement of the cells.
"The basic idea is to use imaging as a method to see some of the physical parameters in cancer biology," Liu says. "Instead of only being able to look at millions of cells at time, technology has enabled us to examine a single cell. When the system is going smaller and smaller, the physical parameters inside the biological system become more and more useful and more and more important."
Full details of the work appear in the journal Scientific Reports.