Scientists capture first atomic-scale ‘movie’ of microtubules forming

When one cell begins to multiply, parts of the cell jump into action. Each chromosome duplicates its genetic information, and then moves to the middle of the cell. Then, lasso-like microtubules hook the duplicated chromosomes and rip them apart as the cell splits into two.

This is the kind of thing you learn in high school biology. But scientists didn’t have much understanding of how this lasso of the cell begins forming.

“The cell, in a very remarkable way, quickly sprouts from its two ends large tubes that hook the chromosomes and pull each of the copies towards the two poles of the cell. Only then is it possible to encapsulate a copy of all our genetic material in each daughter cell,” said Óscar Llorca, a structural biologist at the Spanish National Cancer Research Center (CNIO).

“That’s why we say that microtubules play a key role in cell division. We need to understand very well the mechanisms that trigger the formation of these microtubules, at the right place and at the right time.”

To do that, the researchers had to go small and slow. When they’re full size, microtubules are a thousandth of a millimetre long and a few nanometres in diameter, but when they’re first forming, they’re even smaller.

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Credit: Underbau/CNIO

Plus, these early stages of microtubule construction occur at incredibly high speeds, so to observe what was happening on a Total Internal Reflection Fluorescence (TIRF) microscope, the team had to slow down the process.

“We had to find conditions that allowed us to image over a million microtubules in the process of nucleation before they grow too long and obscure the action,” explains Cláudia Brito, a postdoctoral researcher at the CRG and first author of the study.

“We were able to achieve this using the molecular toolbox of our lab and then freeze the microtubule stubs in place.”

The team took millions of photos of these microtubules at these arrested stages of growth, and then arranged them in the right order to see the rods form. This created a type of movie. However, so that some poor PhD student didn’t have to put millions of these images in order, they turned to AI.

“Determining the three-dimensional structure of growing microtubules from microscope images has been extremely complex. We needed multiple digital image-processing tools,” explains Marina Serna, CNIO researcher.

This ‘movie’ has allowed researchers to understand how the microtubule formation starts.

Scientists were already aware of several proteins called g TuRC, which starts life as an open ring. This is not able to form the classic microtubule rod shape. But the study shows that just one piece of the microtubule causes g TuRC to close and form a ring for the rest of the pieces to attach to.

“That’s the trick the cell uses to close  g TuRC,” explains Llorca.

“As soon as this first brick enters, a region of g TuRC is able to hook it and, like a loop, acts as a latch that pulls the ring closed and launches the process.”

The research has been published in Science.

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