Collective dynamics of flexible active particles on substrates: from cells to tissues

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Collective dynamics of flexible active particles on substrates : from cells to tissues

Publication . Estevão Pereira Pinto, Diogo; Araújo, Nuno; Gama, Margarida Telo da

We study the effects of disorder in epithelial confluent tissues through the Voronoi model for dense tissues. The modeling of epithelial tissues relies on three different mechanisms: cell-cell and cell-medium interactions, and propulsion or activity. First, we focus on the role of cell-cell interaction in this model by exploring, in the athermal limit, its anomalous jamming behavior. We introduce a new metric that allows us to find a hierarchical structure in its energy landscape similar to colloidal particle systems. We then introduce a cell-medium interaction by explicitly considering an interaction between the cells and their underlying substrate. We consider that the targeted geometry of the cells changes according to their spatial position and in turn affects the cells motility. We show that when the characteristic length scale of the disorder is smaller than the cell size, the cell motility increases when compared to its homogeneous counterpart. This result is in sharp contrast to what has been reported for tissues with heterogeneity in the mechanical properties of the individual cells, where the disorder favors rigidity. Due to the internal biological complexity of the cells, changes to the cell-substrate interaction should trigger a hierarchy of biochemical responses in the cell that lead to its adaptation to the new substrate region. As such, the process of cell adaptation to its underlying structure is not instantaneous but requires a finite time that in many cases competes with other relevant timescales for the dynamics such as, for example, the diffusion timescale. With this in mind, we then introduce a characteristic adaptation time of the cells to the cell-substrate interaction changes. We study how the competition between the adaptation of the cells and their mobility can compromise the fidelity of the substrate and by relating this with the previous disordered substrate propose a typical time scale for the adaptation of cells that is relevant for experiments. Lastly, we consider non-confluent tissues by allowing the cells to break from one another and create empty spaces. This change opens the door to the study of the surface properties of cell colonies and it is a first step towards the study of the transition from a single cell to confluent tissue. Implications of our findings in the field of Soft Condensed Matter Physics are discussed.

2022-02Tese de doutoramento

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Entidade financiadora

Fundação para a Ciência e a Tecnologia

Programa de financiamento

OE

Número da atribuição

SFRH/BD/131158/2017