EMBL researchers have developed an advanced microscope that lets scientists observe the mechanical properties of developing embryos in real time. This new approach provides unprecedented speed and detail, offering fresh insights into how tissues form and change.
- Scientists have created a high-speed method to study the mechanical properties of developing embryos with unmatched precision.
- The technique, called line-scanning Brillouin microscopy (LSBM), builds on Brillouin scattering—a process where light interacts with a material’s natural thermal vibrations.
- By leveraging this phenomenon, LSBM enables researchers to map tissue mechanics without physically touching or disturbing the sample.
The Hidden Physics of Light and Matter
In 1922, French physicist Léon Brillouin described a fascinating effect: when light interacts with a material, it exchanges energy with the material’s natural thermal vibrations. This energy exchange alters how the light is scattered. By analyzing the spectrum (or color) of the scattered light, scientists can uncover key physical properties of the material.
More than a century later, researchers from the Prevedel group at EMBL, in collaboration with others, have applied this principle — known as Brillouin scattering — to study the mechanical properties of developing embryos with remarkable speed and precision.
The Mechanical Lives of Cells
“We often tend to think of cells or tissues only in terms of their biological properties – which genes do they express? Which biochemical pathways do they rely on? What chemical signals do they send to each other?” said Robert Prevedel, Group Leader at EMBL Heidelberg. “However, cells and tissues also have rich ‘mechanical’ lives. And these physical properties can help determine their biological function.”
The physical forces cells experience and their own material properties play a critical role in processes as diverse as embryonic development, tissue integrity, and the pathophysiology of diseases such as cancer. Two of these properties are viscosity – a measure of how easily a substance flows – and elasticity – a measure of how quickly a deformed object returns to its original state.
Overcoming the Challenges of Brillouin Microscopy
However, measuring these properties without damaging the cells and tissues can be challenging, as measurement methods often involve invasive approaches like ‘poking’ or ‘probing’ the samples in different ways. Here, as researchers have previously shown, microscopy based on Brillouin scattering can be useful for non-invasively viewing and assessing tissue mechanics.
Unfortunately, traditional Brillouin microscopy suffers from a few drawbacks. First, the speed of imaging is slow, since the method relies on collecting information from a single point on the sample at a time. Second, many biological tissues and cells are highly sensitive to light, and as a result, the long light exposures required in Brillouin microscopy can harm or deter the very processes that scientists wish to study.
A Faster, More Powerful Imaging Method
In their new study published in Nature Methods, Prevedel and his colleagues describe a new microscopy method based on Brillouin scattering, that deals with the above challenges in innovative ways. Researchers in the Prevedel group are experts in developing advanced optical imaging techniques and pushing the frontiers of deep tissue microscopy.
As Carlo Bevilacqua, PhD student in the Prevedel lab and first author of the study, explains, the new method, called line-scanning Brillouin microscopy (LSBM), provides three major advantages.
First, instead of collecting information from a single point at a time, the new microscope scans the sample using an entire line of light at a time, which increases the speed of imaging by at least a hundred times. Second, it uses a new optical geometry, near-infrared light, and a Rubidium cell to significantly increase the signal-to-noise ratio, providing better resolution and reducing the risk of light-induced damage to cells.
And third, by integrating this system with an advanced light-sheet microscope, scientists can simultaneously visualise biomolecules using fluorescence, and this information can be layered on top of the mechanical properties of tissues.
“I really like building things,” said Bevilacqua. “Setting up a microscope like this involves quite a bit of theoretical optics knowledge, coupled with engineering and hands-on work, but you also require biological know-how.”
A Window Into Embryonic Development
As proof of principle, the scientists used their newly built microscope to study embryonic development in three animal species from different evolutionary branches of the tree of life – fruit flies, mice, and a marine organism called Phallusia mammillata. In all of these species, the new microscopy method allowed researchers to follow the dynamics of mechanical changes in developing embryos in three dimensions and over a time scale of many hours.
“Studying development like this, in real time and in the whole volume of tissues rather than just the surface, can reveal many new and interesting biological mechanisms,” said Juan Manuel Gomez, postdoc in the Leptin and Prevedel labs and second author of the study.
The Power of Collaboration and Recognition
The study involved collaborations with multiple other groups at EMBL, including the Ellenberg and Diz-Muñoz groups, as well as EMBL alumna Maria Leptin, formerly the director of EMBO and currently the European Research Council (ERC) President.
This method was also selected as one of The Guardian’s 10 biggest science stories of 2022. “That was a big surprise; I definitely didn’t see it coming,” said Prevedel. “I think it really shows the potential of the method, and the growing recognition of the importance of understanding how the biomechanical properties of tissues influence their function.”
Reference: “High-resolution line-scan Brillouin microscopy for live imaging of mechanical properties during embryo development” by Carlo Bevilacqua, Juan Manuel Gomez, Ulla-Maj Fiuza, Chii Jou Chan, Ling Wang, Sebastian Hambura, Manuel Eguren, Jan Ellenberg, Alba Diz-Muñoz, Maria Leptin and Robert Prevedel, 30 March 2023, Nature Methods.
DOI: 10.1038/s41592-023-01822-1
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