In hot pursuit

29 April 2020:

A host of diseases – like meningitis, diabetes, cystic fibrosis, Alzheimer’s disease, even some cancers – are ultimately caused by problems at the cellular level. Hence, understanding what is happening inside cells is essential. Observing cells under a microscope helps, but what medical researchers would really like to do is see processes inside cells in minute detail.

One way to do this is to identify temperature changes within a cell, right down to individual cellular organs, or organelles. As they turn on and off, proteins, molecular motors and organelles like mitochondria – the power packs of cells – rise and fall slightly in temperature. But little of this is discernible visually.

“There is still a lot to learn about how the temperature of a cell varies, in particular as a function of when it’s happy, when it’s stressed, or as it goes through different processes,” said Prof Andrew Greentree, chief investigator for theory and modelling at CNBP’s RMIT University node in Melbourne. “Can we measure the difference between metabolic activity of different types of cells, for example?”

Greentree’s team provides a quantum approach to imaging and sensor problems faced by biologists and clinicians. That’s how, working with CNBP colleagues in Adelaide, Greentree and his team developed a microscope slide that can accurately map temperature changes within cells grown on it.

Andy Greentree in the lab

The slide, made of lanthanide-doped tellurite glass, changes its fluorescence with temperature and, in research awaiting publication, the researchers have proven that tiny changes in temperature can be detected, tracked and mapped as they occur.  This work builds on earlier successes from the group of Professor Heike Ebendorff-Heidepriem, who built temperature sensing optical fibres using the same glass technology.

“The whole cell is only about 10-15 microns (0.01 to 0.015 mm) across and we can map temperatures down to 1-micron increments, right underneath the cell,” said Daniel Stavrevski, a student working on the project. “As mitochondria generate energy for the cells, they get hotter. It’s quite an astonishing thing to see.” Even the best thermal cameras can only resolve objects around 10 microns in size, “but they sacrifice temporal resolution which is important when you want to monitor the activity of a mitochondria which could be as fast as milliseconds.  So getting down to 1 micron – and maybe going smaller – will uncover new science,” he added.

Having proved they can map temperature in skin cells, they plan to expand imaging to other types of cells, which have higher metabolic activity, and should therefore show greater temperature ranges.

An additional goal is to combine the slides with thermophores – probes which fluoresce in the presence of heat –to build 3D heat maps that sense temperature changes in real time.

It’s pioneering work, with potential to give insight into all sorts of metabolic functions inside cells as they occur, potentially tracking cells and organelles as they divide, grow, interact, and carry out other vital tasks. Greentree explains: “To see fundamental physics as it guides life, that’s why we do science”.