A kinetic mechanism for cell sorting based on local variations in cell motility

Cell sorting.

Our current understanding of cell sorting relies on physical di fference, either in the interfacial properties or motile force, between cell types. But is such asymmetry a prerequisite for cell sorting? We test this using a minimal model in which the two cell populations are identical with respect to their physical properties and di erences in motility arise solely from how cells interact with their surroundings. The model resembles the Schelling model used in social sciences to study segregation phenomena at the scale of societies. Our results demonstrate that segregation can emerge solely from cell motility being a dynamic property that changes in response to the local environment of the cell, but that additional mechanisms are necessary to reproduce the envelopment behavior observed in vitro. The time course of segregation follows a power-law, in agreement with the scaling reported from experiment and in other models of motility-driven segregation.


Asymmetric Segregation of Damaged Cellular Components in Spatially Structured Multicellular Organisms

Damage accumulation in a system of spatially ordered cells with symmetric and asymmetric replication, respectively.

The asymmetric distribution of damaged cellular components has been observed in species ranging from fission yeast to humans. To study the potential advantages of damage segregation, we have developed a mathematical model describing ageing mammalian tissue, that is, a multicellular system of somatic cells that do not rejuvenate at cell division. To illustrate the applicability of the model, we specifically consider damage incurred by mutations to mitochondrial DNA, which are thought to be implicated in the mammalian ageing process. We show analytically that the asymmetric distribution of damaged cellular components reduces the overall damage level and increases the longevity of the cell population. Motivated by the experimental reports of damage segregation in human embryonic stem cells, dividing symmetrically with respect to cell-fate, we extend the model to consider spatially structured systems of cells. Imposing spatial structure reduces, but does not eliminate, the advantage of asymmetric division over symmetric division. The results suggest that damage partitioning could be a common strategy for reducing the accumulation of damage in a wider range of cell types than previously thought.

The work was a collaboration with Jeppe Juul and Kristian Moss Bendtsen at Center for Models of Life, University of Copenhagen.

The article is available here.