A new way of chemically labeling live cells with high spatial and temporal precision using light has been developed by researchers from Harvard University and the Chinese Academy of Medical Sciences. The study, published in ACS Chemical Biology, introduces "photo-click adapters" that integrate light-based control into common chemical labeling techniques. This breakthrough enables precise and dynamic multicolor cell labeling that offers new ways to track biological processes in cells and tissues in great detail.
Making biology visible
Cell labeling is an essential tool in biological research, allowing scientists to track cells, study their behavior, and analyze biochemical reactions and interactions. Many techniques for labeling cells use genetic encoding or chemical recognition to provide specificity. However, despite this, these methods often lack the spatial and temporal precision required for tracking many of the dynamic biological processes that occur in cells and tissues. The team of researchers led by Adam E. Cohen, professor of Chemistry, Chemical Biology, and Physics at Harvard University, have come up with a solution for this problem by adding a light-gating element to commonly used live cell labeling methodologies. The light-gating element lets the researchers precisely control when and in which part of a cell or tissue that the labeling will be activated.
Cell-level labeling
Cohen and coworker were able to construct this light-gating function using photocaged tetrazines, a type of molecule that remains inactive until exposed to light. This modification, which the researchers call “photo-click adaptor”, provides a way to switch the cell label from a caged and inactive state to an uncaged and active state. Once in the uncaged state, the tetrazines can react quickly with alkenes through a so-called “photocklick” reaction, making it possible to for instance add fluorescent dyes specifically to the light-activated parts of the cell.
To demonstrate the principles behind this new photolabeling technique, Cohen and his team selectively illuminated parts of labeled cells to activate the photo-click adaptors in the selected regions. They then used BioPen to add fluorescent dyes, modified to only bind to the activated adaptors, to individual cells. Their results show that the fluorescent dyes only bound to the regions that had had been activated using light.
New ways to trace biology
The research team also wanted to explore possible applications for the technique and therefore tested their method in live zebrafish embryos, showing that it could be used to track tissue movements during embryo development. They also explored how the technology could enable multicolor labeling and live-cell sorting, allowing researchers to distinguish and separate different cell populations based on optical patterns. With these two experiments as demonstrations, Cohen and team envision a number of future applications for the photo-click labeling technology, including high-resolution dynamic tracking of proteins within cells, optical phenotypic screening connected to downstream omics, and red-shifted switching possibilities that enables deeper tissue penetration and reduced phototoxicity.
We are very happy that the team of scientists have chosen to use BioPen in their work and look forward to following their future research efforts.
The article Tools for Intersectional Optical and Chemical Tagging on Cell Surfaces is available through the ACS Chemical Biology website.