Much like the mimosa plant’s leaves closing with a gentle touch, human cells react to mechanical stimuli, converting them into electrochemical signals that influence everything from tissue growth to disease progression.
“Understanding how cells respond to mechanical stress can inform tissue engineering and regenerative medicine to help model diseases like cancer or heart conditions, where abnormal mechanical environments influence cell behaviour,” explained Boon Seng Soh, a Principal Investigator at the A*STAR Institute of Molecular and Cell Biology (A*STAR IMCB).
To study how these forces shape cells, scientists typically rely on comparing pre- and post-stress images, but such indirect methods often miss subtleties in complex three-dimensional structures like organoids, Soh explained.
Tackling this limitation, Soh collaborated with Yu-Cheng Chen and Guocheng Fang from Nanyang Technological University, Singapore; and researchers from the Chinese Academy of Sciences, China, to create an innovative mechanosensitive sensor. This new tool was designed to enable real-time, high-resolution tracking of mechanical stress in organoids, to break new ground in understanding cell mechanics.
Their approach involves tiny, compressible hollow microlasers made from poly(lactic-co-glycolic acid) (PLGA), a biodegradable polymer. These microscopic spheres, less than a hundredth the width of a strand of human hair, featured ultrathin shells dotted with micropores. In a series of tests, the team demonstrated the microlasers’ precision, sensitivity and fast response time, revealing their potential for dynamic stress measurements.
“The miniaturised size of these microlasers allows for direct embedding within organoids, enabling real-time, non-invasive monitoring of cellular responses to drugs,” Soh explained. With high sensitivity to even the smallest environmental changes, these microlasers preserve organoid structure throughout the analysis.
As a proof of concept, the researchers embedded their microlasers within 3D tumour cell cultures. This new technology allowed them to map the varying mechanical responses of lung tumouroids to nine anti-cancer drugs that induce stress in cells. They further demonstrated its effectiveness by tracking contractile stress in 3D heart organoids, observing shifts in the heartbeat-like contractions after exposure to drugs used for high blood pressure and heart failure.
“This approach offers a more precise, localised measurement of mechanical forces, providing deeper insights into how mechanical stress influences organoid development and function,” said Soh.
Soh’s team sees future iterations of their microlasers playing a big role in speeding up drug testing, potentially allowing heart disease treatments to be tested across many organoids at once. They also plan to incorporate machine learning to sift through the massive amounts of real-time data generated in the process.
The A*STAR-affiliated researchers contributing to this research are from the A*STAR Institute of Molecular and Cell Biology (A*STAR IMCB).
