A new nanoscopy technique developed at The Australian National University (ANU) has uncovered networks used for communication between cells, which researchers say could open new ways to understand human diseases.
Published in Nature Communications, the technique is designed to allow researchers to observe how living cells interact with their environment over several days, revealing three-dimensional behaviours that were previously difficult to see with conventional microscopes.
“Using gentle, label-free imaging means we can finally witness the secret, dynamic life of cells in real time and 3D,” said senior investigator Dr Steve Lee from the John Curtin School of Medical Research (JCSMR) at ANU.
“The technique allows for faster and more accurate breakthroughs in how we understand and treat human disease at the nanoscale.”
The team said it used the method, known as RO-iSCAT, to observe thin, thread-like nanoscale extensions from cells. Over days of continuous imaging, the structures were seen extending, retracting and reconnecting, forming networks that transfer biochemical messages to neighbouring cells.
Lead author and PhD researcher Junyu Liu said the technique was developed by rotating the angle of light illuminating the sample and combining images at different heights.
“Under rotational illumination, the background noise is stripped away, revealing various nanoscale cellular structures in three dimensions,” Mr Liu said.
According to the researchers, the work focuses on tracking thread-like cellular nanoscale extensions that are important for cellular signalling, communication and movement. Dr Lee said the method increases the detected light signal in real time and does not require chemical dyes or “labels”, which are commonly used in nanoscopy but can introduce phototoxicity.
Footage from the research suggested the connections are not static, with the structures twisting around each other before forming a stable bridge, the team said.
ANU said Dr Daniel Lim, a senior imaging scientist on the team, used the technique to investigate different cell types, including pancreatic cancer cells and human blood vessel cells, examining how they form multiple “tight” bridges with surrounding connective tissue cells. The researchers said these interactions are thought to help tumours grow and resist treatment by shaping the local environment, or assist in forming new blood cells.
The researchers said the same approach could also help scientists understand how viruses move between cells, as some are thought to spread through cellular bridges.
“Now we have the tool to better understand these nanoscale interactions within larger cell populations,” Dr Lim said.
“This could help us learn how to block specific pathways to treat diseases or deliver drug therapies more precisely.”
The paper, Using rotational integration of oblique interferometric scattering to track axial spatiotemporal responses of tubular membrane protrusions, is published in Nature Communications.
