Multicolor electron microscopy reveals proteins and cell structure with nanoscale decision

Scientists fill developed a original imaging approach that leverages a novel distinction mechanism in bioimaging to mix the strengths of two highly effective microscopy strategies, permitting researchers to see each the advanced structure of cells and the particular areas of proteins – all in vivid colours and at nanometer-scale decision.

The breakthrough, referred to as multicolor electron microscopy, addresses a long-standing problem in organic imaging: Scientists fill historically had to make a choice from high-quality structural particulars or monitoring particular molecules, however not each at the identical time.

The method opens doorways to the examine of all issues Cell signaling to prepare molecular clusters inside cells, whereas at the identical time seeing precisely the place these processes purchase space throughout the cell structure. The analysis will probably be offered on the seventieth Annual Assembly of the Biophysical Society, February 21-25, 2026, in San Francisco.

I fill at all times been fascinated by creating original microscopy strategies that may picture issues we fill not seen earlier than. We’re constructing a multicolor electron microscope – a method that mixes the benefits of electron microscopy and fluorescence microscopy.”

Debsankar Saha Roy, a postdoctoral researcher in Maxim Prigozhin’s lab at Harvard College

Conventional fluorescence microscopy entails attaching glowing tags to proteins of curiosity after which shining seen mild onto the pattern to design these tags glow. This method is great for locating particular molecules, however has important limitations. “The decision is proscribed to round 250 to 300 nanometers, so you’ll be able to’t see particular person proteins clearly,” explains Roy. “However the larger drawback is that you just do not see the construction of the cell. You see no matter is labeled, however you do not see all the pieces else round it.”

Electron microscopy, alternatively, can reveal mobile buildings in beautiful element all the way down to just a few nanometers, however has historically been unable to establish particular molecules by shade. Scientists fill tried to mix the 2 approaches by taking separate photographs utilizing every technique after which overlaying them. Nevertheless, precisely aligning the pictures proved extraordinarily tough, particularly with giant samples comparable to mind tissue.

The Harvard crew’s resolution is elegant: As a substitute of utilizing two separate imaging periods, they consume a single electron beam to conclude each duties at the identical time.

“We’re not sending mild, we’re sending a beam of electrons,” Roy mentioned. “We fill probes you could connect to a protein that emit seen mild when excited by electrons. This course of is known as cathodoluminescence. So from the identical electron beam you regain two varieties of data: the coloured sign from the probes and in addition the detailed structural picture of the electrons.”

A key benefit of the approach is that researchers can consume present fluorescent dyes which might be already broadly used and nicely characterised. The crew had beforehand developed lanthanide nanoparticles as probes for multicolor electron microscopy and labored to bind them to proteins.

Just lately, the crew made a stunning discovery after they positioned some frequent fluorescent dyes within the electron microscope. “Probably the most stunning factor we noticed was that normal dyes utilized in fluorescence microscopy additionally emit seen mild when excited with electrons,” Roy mentioned. “This has by no means been finished earlier than. And these dyes – and their strategies of protein labeling – are already developed and accessible; there isn’t a must develop something original.”

The crew has already proven that the approach works in mammalian cells and organic tissues, together with fungal-infected flies.

Trying to the long run, the researchers wish to broaden the know-how to a few dimensions. The method presently produces flat, two-dimensional photographs. The subsequent problem is adapting to cryo-electron microscopy – a method that snap-freezes samples, preserving cells of their pure state and permitting scientists to picture them from a number of angles to create 3D reconstructions.

“We would like to prolong this multicolor electron microscopy method to 3D,” Roy mentioned. “To regain there, we would like to implement this system in ultrathin sections of cell-embedded matrices and/or in cryo-electron microscopy – that’s the following step.”