Advances in materials science, cell biology, and imaging are combining to create tools that will allow researchers to track in real time and in super-fine resolution what happens inside a single cell.
Being able to visualise cellular processes as they happen is seen as a critical part understanding what changes occur when disease strikes and how that process could be prevented, reversed or otherwise cured.
For many decades, scientists have relied on using dye molecules that are absorbed into cells to visualise their behaviour. These dye molecules, originally adapted from the dyes used in the textile industry, have undergone development and improvement, but their basic principles and properties remain largely the same. A major drawback is dimming or fading of the dyes as they’re exposed to the high-intensity light for imaging. Scientists have only a small window of time to image the cell, creating a snapshot of cellular events rather than ongoing, real-time tracking.
Meanwhile, molecular imaging and microscopy have advanced to the point where super-fine resolution and real-time imaging is possible, not only at a whole-cell level, but within a cell and of its various components.
This is inspiring microbiologists to team up with materials engineers to develop new luminescent bio-materials that, like an aircraft beacon, allow scientists to track and visualise cellular processes without adversely impacting the living cell.
Figure 1 Application of luminescent nanoparticles with different sizes in super resolution and single molecule tracing (Nature Methods 2018).
In a paper published today (30 May) in the journal Nature Methods, Prof. Peng Xi from College of Engineering, Peking University, together with researchers from University of Technology Sydney (UTS) and the University of Wollongong (UOW), and the University of G?ttingen, Germany, have outlined how light-emitting probes might be applied by life scientists in visualising cellular processes.
“Conventional organic fluorescent dyes cannot meet the multifaceted requirements of super-resolution and dynamic tracking. These openings can be fulfilled through the development of artificial nanoparticles, to lead the visualizing of subcellular organelles to next level.” said Peng Xi, a professor and expert in super-resolution microscopy from Peking University.
Lead author Distinguished Professor Dayong Jin from UTS said materials scientists have made tremendous progress in the development of novel structures that are extremely small – comparable to the size of a protein molecule – that emit light with greater brightness and precision than classical dye molecules.
“We can take nanomaterials, such as light-emitting plastic or ceramic particles, and deliver them to the site in question. Various other techniques help the particle to pass through the cell wall and we can visualise what is going on inside the molecular machinery.
“We have noted advances such as the ability to measure the changes in transport within a neuron as a result of brain disease,” Professor Jin said. “These advanced particles also make it possible to use different colours and pulse signals simultaneously so we can in effect visually barcode genes or proteins to see how these are translated and transcribed - the encoding of life itself.
“This is an exciting time for the cell biology and materials science communities who now have an unprecedented opportunity to explore cellular imaging with unprecedented accuracy and resolution.
Co-author Distinguished Professor Antoine van Oijen, who leads UOW’s Molecular Horizons initiative, said the article highlighted how bringing the materials science community together with scientists from the life sciences would be critical in illuminating the intricate details of how life works.
“Understanding of disease processes, and thus development of cures, relies on us understanding cellular processes: how do the various biomolecules inside our cells do their jobs? What happens when they stop doing their jobs properly and disease strikes?”
In order to achieve the above missions, in Huairou, Beijing, Peking University is leading the construction of a multi-scale, multi-modality imaging facility with a national investment of 1.75 billion Yuan, which will span across 10 orders of magnitude in biology, and cover from meter (the size of human body) to Arstron (the size of a molecule), to study the occurrence and development of disease at different scales, through the strategic combination of a variety of microscopic techniques. For the first time, the disease can be studied in its full depth and scale. Coincidentally, at the University of Wollongong, Australia, Professor Antoine van Oijen is leading the construction of the "Molecular Horizons" (https://www.uow.edu.au/molecular-horizons/UOW240124.html), an investment of 80 million Australian research facility. The mission of this facility is to provide researchers with new molecular-level visualization of biological processes, thereby unlocking the deepest secrets of cells and developing new methods for detecting and attacking diseases.
Peng Xi and Dayong Jin acknowledge the funding support from National Science and Foundation China, under grant “High throughput upconversion nanoparticle super-resolution microscopy and single particle tracking” (61729501).