UBC Okanagan researchers have made two major discoveries that could revolutionize the way scientists observe and measure the molecular forces within living cells.
The discoveries could change the way scientists understand the mechanics of life and lead to new breakthroughs in cancer research, immunology and regenerative medicine, according to UBCO's Dr. Isaac Li.
Recently published in Advanced Science and Angewandte Chemie — two leading scientific journals — the discoveries offer unprecedented precision and durability in force imaging which could significantly advance the field of molecular mechanobiology, says Li, associate professor of chemistry at the Irving K. Barber Faculty of Science.
Led by Li, the Canada research chair in single-molecule biophysics and mechanobiology, the research team created qtPAINT, a groundbreaking imaging technology. It's the first imaging method that can measure molecular forces with nanometre-level spacial precision and minute-scale time resolution. The technology works by combining DNA-based molecular tension probes with advanced microscopes, giving researchers a clearer view of how tiny mechanical forces behave inside living cells in real time.
“Tiny molecular forces drive many important functions in the body, like fighting infections, healing wounds and cancer progression,” explains Dr. Seongho Kim, lead author of the qtPAINT study. “Before qtPAINT, researchers could see where these forces were happening, but we couldn’t measure how strong they were or how they changed over time.”
Following the success of qtPAINT, Li's team tackled a longstanding challenge that limited the use of DNA-based tension probes. This challenge was the rapid degradation of the probes by natural enzymes called DNases. As Li explains, tension probes help scientists watch and measure the minuscule forces taking place within cells in real time, revealing how they communicate and behave.
The team's second paper introduces a simple yet powerful solution called Decoy DNA, where extra strands of harmless DNA are added to experiments to act as sacrificial targets for DNases. This approach significantly extends the lifespan of functional tension probes from just a few hours to more than 24 hours, or even several days. It in turn greatly improves the stability and accuracy of cellular force measurements, says Hongyuan Zhang, lead author of the Decoy DNA study.
“Rather than using complex and costly chemical modifications, our approach is more like distracting predators with these decoys,” says Zhang. This protects our DNA probes and significantly improves the quality and duration of our measurements.”
Li's lab specializes in single-molecule biophysics and mechanobiology, developing advanced methods to visualize and manipulate molecular forces within living cells. It takes an interdisciplinary approach, combining cell biology, biochemistry, biophysics, nanotechnology and bioengineering to create unique platforms for scientific discoveries.
“Our goal has always been to develop effective and accessible tools,” said Li. “These studies reflect our ongoing effort to develop technologies that support meaningful discoveries across many areas of science.”
