During the growth of embryos cells align with forces from the surrounding tissue. These forces originate from differences in growth rates, muscle contractions or gravity. Researchers at the CWI research centre in Amsterdam now showed for the first time with a mathematical model that active cell contractions can accelerate and facilitate this reorientation of cells. The force exerted by the cell itself can also make the formation of strings of cells in the direction of the stretching more easily. The scientific simulations predict that the interplay between internal and external forces can make the difference between the development of, for example, either muscle-like tissue or vascular networks. Their research was recently published in the leading Biophysical Journal (112).
PhD student Lisanne Rens (CWI) says: "After the first cell division tissues are created, such as bones and blood vessels, or organs, such as a heart and lungs. But how do these cells know where precisely the lung cells should be, with a behaviour very different from heart cells? This is partly in the genes, but physical forces also play a role. We want to understand what makes cells move and start growing in the direction of stretching forces from their environment. "
She continues: "We have developed a hybrid computer model, based on the 'Cellular Potts Model', which we use to describe the cells. We have linked this to a ‘finite element ‘ model describing the gelatinous environment in which the cells live: the 'matrix'. We simulate both the stretching forces of the environment and the forces applied by the cells themselves. They do not only undergo this passively but they can also actively respond to external force. Because cells pull at the matrix they amplify the tension that is already there. "
The developed mathematical techniques and insights can be applied in the design of artificial tissues (tissue engineering) such as organs, skin, or in applications such as in-vitro meat. The research was conducted in the Life Sciences Group at the Centrum Wiskunde & Informatica (CWI) research centre in Amsterdam, the Netherlands, and it was funded by the NWO Vidi project of Prof. Roeland Merks (CWI and Leiden University). SURFSara helped with the computing power.
The article ‘Cell Contractility Facilitates Alignment of Cells and Tissues to Static Uniaxial Stretch’ by Elisabeth G. Rens (CWI) and Roeland M.H. Merks (CWI and UL) appeared in Biophysical Journal, Volume 112, Issue 4, 28 February 2017, pp. 755-766. See also: <u>http://dx.doi.org/10.1016/j.bpj.2016.12.012 or </u>https://arxiv.org/abs/1605.03987<u> (open access).</u>