Explaining the stripes of the zebra (article in Cell Systems by Kavli/Delft-BN researchers Théo Maire and Hyun Youk)


By: TUDelft/webcommunication
Researchers from Delft University of Technology have made steps to explain how spatial patterns, like the stripes on a zebra, emerge in a population of cells. This enables them to predict certain spatial patterns without having complete information about what each of the millions of cells are doing. The researchers published their findings in Cell Systems on 25 November 2015.

Mathematical rules
Cells are composed of many different genes, proteins and other molecular parts. To make matters even more complicated, putting multiple cells together creates tissues and whole organisms such as human beings.

‘One of the major challenges that scientists face in modern biology and physics is somehow unravelling this complexity into ‘simple’ mathematical rules, like those of physics, that underlie and tie together disparate and complex living systems’, says Dr Hyun Youk, researcher at Delft University of Technology and the senior author of the publication in Cell Systems. ‘Motivated by previous experimental findings, we have now derived some mathematical rules that govern a wide range of multicellular systems.’

Talking cells
Youk and his former Master’s student and the first author of the work, Théo Maire, looked at a relatively simple class of cells that can both secrete and sense one particular molecule. This molecule can turn ‘on’ or turn ‘off’ a specific property of such a cell. ‘We show how putting two such cells together, and making them communicate with each other (through this molecule), alters each cell’s behaviour. We repeat this by putting together more and more cells that ‘talk’ to each other through this signalling molecule.’

‘We have derived rules with which we can now predict the emergence of certain spatial patterns in a group of cells.  This could enable us to explain how spatial patterns (such as the stripes on a zebra) emerge in a population of cells, without us having the complete information about what each of the millions of cells are doing.’

Amount of freedom
Maire and Youk can now trace step-by-step, how complex behaviours of tissues and embryos can emerge from the simple interactions inside and between cells. ‘Our work thus explains a wide class of different biological entities that are important to the development and functioning of tissues and organs. We are able to show for the first time that concepts such as a cell’s ‘amount of freedom’, ‘amount of autonomy’, and ‘amount of collectiveness’ are quantifiable traits.’

Maire and Youk are also introducing the concept of  ‘entropy of population’, a concept that can finally explain how spatial patterns emerge in a population of cells without having complete information about what each of the millions of cells are doing. This new concept makes a connection between disorderliness and orderliness of cells, with a new form of entropy that may be compared to the concept of entropy known in physics. This opens a door for exploring this intriguing link in more depth in the future.’

Cartoon image of cells collectively spelling "ENTROPY" with varying orderliness. Here Maire and Youk are formally defining the amounts of autonomy and collectiveness of cells. Highly collective cells (beads of same color) form ordered patterns (the letter "E"). Highly autonomous cells (beads of different colors) form disordered patterns (the letter "Y"). An autonomy-collective spectrum (depicted by progressively jumbling letters) determines the "entropy of population", gauging the cell population's ability to form disorder (represented by each letter's height).

More information 
Théo Maire, Hyun Youk: "Molecular-level tuning of cellular autonomy controls the collective behaviors of cell populations", Cell Systems, 25 November 2015.