The process of cell division is central to life. The last stage, when two daughter cells split from each other, has fascinated scientists since the dawn of cell biology in the Victorian era. For just as long, it has been notoriously difficult to study this final step, when the dividing cell creates a furrow before cleaving in two.

Both the cell-free egg extract system and embryos recruit critical signaling molecules necessary for cytokinesis signaling. In these micrographs, fluorescently labeled microtubules are green and Aurora B, the cytokinesis signal, is red. Images: Mitchison Lab

Both the cell-free egg extract system and embryos recruit critical signaling molecules necessary for cytokinesis signaling. In these micrographs, fluorescently labeled microtubules are green and Aurora B, the cytokinesis signal, is red. Images: Mitchison Lab

The name given to this process by those early biologists, cytokinesis, translates as "cell movement" and captures the sense of a highly active and organized series of events. Scientists have now learned much more about the proteins involved and their behavior, and yet a central mystery remains: How does the cell signal where the furrow should be?  

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There is a simple reason for that blind spot: It’s hard to see and test such a complex feat in living cells. Now Harvard Medical School systems biologists report in Science that they have reconstituted cytokinesis—complete with signals that direct molecular traffic—without the cell. Combining frog-egg extracts with lipid membranes that mimic the membrane of the cell, they built a cell-free system that recapitulates how the cleavage furrow is assembled.

This cell-free system has two huge advantages: It expands the scale of the furrow-building events, making them easier to see, and it gives the researchers an easy way to manipulate the proteins involved. Quickly removing and returning proteins to see how changes in the molecular players affect cytokinesis is impossible when the cell is whole, but easy when the cellular innards are spread out on a microscope slide.  

The key challenge, though, was that the behavior of cytokinesis is entirely dependent on having a membrane to furrow—and membranes are exactly what have to be removed to make the system cell-free. What made this work possible was the realization that a controlled, flat membrane—made from two layers of artificial lipid supported on glass—could substitute for the curved, constantly moving and complex membrane of the cell.

“We really built what goes on in the cell,” said Timothy Mitchison, the Hasib Sabbagh Professor of Systems Biology at HMS. “We believe our work is a step forward, not only for understanding the assembly of the cleavage furrow but also, more generally, for understanding the biophysics of cytokinesis signaling.”

 

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