Biology subjects

Kokic, M.

Publications and source records attributed to Kokic, M..

3 recordsLinked to original sources

bioRxiv2019

Cell-based Simulations of Biased Epithelial Lung Growth

During morphogenesis, epithelial tubes elongate. In case of the mammalian lung, biased elongation has been linked to a bias in cell shape and cell division, but it has remained unclear whether a bias in cell shape along the axis of outgrowth is sufficient for biased outgrowth and how it arises. Here, we use our 2D cell-based tissue simulation software LBIBCell to investigate the conditions for biased epithelial outgrowth. We show that the observed bias in cell shape and cell division can result in the observed bias in outgrowth only in case of strong cortical tension, and comparison to biological data suggests that the cortical tension in epithelia is likely sufficient. We explore mechanisms that may result in the observed bias in cell division and cell shapes. To this end, we test the possibility that the surrounding tissue or extracellular matrix acts as a mechanical constraint that biases growth in longitudinal direction. While external compressive forces can result in the observed bias in outgrowth, we find that they do not result in the observed bias in cell shapes. We conclude that other mechanisms must exist that generate the bias in lung epithelial outgrowth.

biophysics↗

bioRxiv2019

Minimisation of surface energy drives apical epithelial organisation and gives rise to Lewis’ law

The packing of cells in epithelia exhibits striking regularities, regardless of the organism and organ. One of these regularities is expressed in Lewis law, which states that the average apical cell area is linearly related to the number of neighbours, such that cells with larger apical area have on average more neighbours. The driving forces behind the almost 100-year old Lewis law have remained elusive. We now provide evidence that the observed apical epithelial packing minimizes surface energy at the intercellular apical adhesion belt. Lewis law emerges because the apical cell surfaces then assume the most regular polygonal shapes within a contiguous lattice, thus minimising the average perimeter per cell, and thereby surface energy. We predict that the linear Lewis law generalizes to a quadratic law if the variability in apical areas is increased beyond what is normally found in epithelia. We confirm this prediction experimentally by generating heterogeneity in cell growth in Drosophila epithelia. Our discovery provides a link between epithelial organisation, cell division and growth and has implications for the general understanding of epithelial dynamics.

biophysics↗

bioRxiv2019

Aboave-Weaire’s law in epithelia results from an angle constraint in contiguous polygonal lattices

It has long been noted that the cell arrangements in epithelia, regardless of their origin, exhibit some striking regularities: first, the average number of cell neighbours at the apical side is (close to) six. Second, the average apical cell area is linearly related to the number of neighbours, such that cells with larger apical area have on average more neighbours, a relation termed Lewis law. Third, Aboav-Weaires (AW) law relates the number of neighbours that a cell has to that of its direct neighbours. While the first rule can be explained with topological constraints in contiguous polygonal lattices, and the second rule (Lewis law) with the minimisation of the lateral contact surface energy, the driving forces behind the AW law have remained elusive. We now show that also the AW law emerges to minimise the lateral contact surface energy in polygonal lattices by driving cells to the most regular polygonal shape, but while Lewis law regulates the side lengths, the AW law controls the angles. We conclude that global apical epithelial organization is the result of energy minimisation under topological constraints.

biophysics↗