Patterns of dancing proteins

The idea that gradients in protein concentrations could lead to natural patterns was put forward by computer pioneer Alan Turing in 1952. Now, scientists in the Cees Dekker La

Zebra’s stripes are perhaps the most visual example of the spatial-temporal patterns that Turing wanted to explain. “Turing, otherwise known from cracking the Enigma code, showed that the reaction kinetics and diffusion of two components could lead to spatial and temporal patterns in biology,” Professor Cees Dekker explained. “The most prominent examples are the stripes on a zebra or the patterns that develop in an embryo.”

Turing himself wrote in his 1952 article The chemical basis of morphogenesis: ‘It is suggested that a system of chemical substances, called morphogens, reacting together and diffusing through a tissue, is adequate to account for the main phenomena of morphogenesis.’

Dekker became interested in protein patterns because a similar mechanism is involved in cell division – a process he’d like to mimic in his artificial cell project. The question was: how does a cell know where exactly to split in half during cell division?

He now knows: “Special proteins shuttle between the poles of the cell. One type attaches to the poles, the other comes in and detaches them, after which they cross over to the other side, and the same happens over and over again. The effect is that these Min-proteins keep away the cell division machinery from the poles to where their concentration is least, namely exactly in the middle.”

In the article that Dekker and his postdoc Dr. Yaron Caspi have now published in the prestigious journal eLIFE, they show what happens if you mix two Min-proteins with ATP as fuel in a fully closed microchamber. Intriguingly, this random mixture spontaneously starts dynamic phenomena where one can see the proteins density fluctuate over time from one part of the chamber to the next. Depending on the dimensions, spontaneous oscillations, traveling waves or spiral rotations will occur.

The elegance of the work conceals much of the hard work behind it. It has cost Caspi, a biophysicist by training from the Weizmann Institute, about ten months to even only purify the proteins that he needed.

After that, he had to develop the chip featuring reservoirs, connector lines, and a reaction chamber. “Originally, I wanted to construct the reactor at about the same size of a bacterium, 4 to 6 micron”, said Caspi over the telephone. “Later, we realised that the proteins behave slightly differently in larger chambers.”

In the end, Caspi has spent more than three years experimenting at the Kavli Institute of Nanoscience at the Faculty of Applied Sciences with precarious results. Breakdowns were manifold, and the work sometimes became tedious. Nonetheless, the tour-de-force article, which is a wrap-up of Caspi’s postdoc project at the Kavli Institute, provides a powerful illustration of the molecular basis of biological patterns, predicted more than half a century previously.

And yet, the result is only a first step. Cees Dekker quoted Francis Crick who commented on Turing’s explanation of the zebra stripes in 1972: ‘Well the stripes are easy. But what about the horse part?’

Green light: Proteins are pumped into the chamber. Red light: the chamber is isolated, movements arise autonomously | Video: Kavli Institute of Nanoscience / Yaron Caspi, Cees Dekker

Proteins behave differently in larger chambers | Video: Kavli Institute of Nanoscience / Yaron Caspi, Cees Dekker

Min oscillations in a life bacterium (in vivo) – Video: Kavli Institute of Nanoscience / Yaron Caspi, Cees Dekker

• Yaron Caspi, Cees Dekker, Mapping out Min protein patterns in fully confined fluidic chambers, eLIFE, November 25, 2016, doi.org/10.7554/eLife.19271

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