Abstract
A precise structural organization of epithelial cells is needed for the proper functioning and development of different tissues. The epithelial cell packing mechanism is associated with mechanical interactions between cells that place the tissue in a state of the lowest mechanical energy. In addition, the planar cell polarity has been recognized as another important mechanism for the epithelial organization that ensures the orientational ordering of the cells. Planar cell polarity is a consequence of an asymmetric distribution of certain transmembrane proteins which is driven by specific intracellular signaling pathways. Mutations and other disruptions of these pathways were found to cause an impaired cytoarchitecture of the epithelium layer. Mutant cells with disrupted activities of signaling proteins basically represent topological defects, which can lead to dysfunctions in tissue operation. Motivated by the fact that regional variations of bond tensions were found in the vicinity of mutant cells, we implement a computational model that combines the tissue development processes following the concept of mechanical energy minimization and the intracellular polarization. Our results reveal that a decrease in mechanical interactions between normal and mutant epithelium cells represents a conceivable regulatory mechanism that diminishes the impact of topological defects caused by mutant cells.
Highlights
Epithelial tissue is constituted by densely packed epithelium cells and has important structural and functional roles throughout embryonic development, morphogenesis, and adult life
We generated several epithelial tissue architectures for different values of line-tension strengths around the mutant cell, as described in Biomechanical Vertex Dynamics Model
Because these mutant cells directly affect the orientation of polarization (Hazelwood and Hancock, 2013) and the structural properties (Classen et al, 2005) of its adjacent cells, the global properties of the developed epithelium depend on both effects
Summary
Epithelial tissue is constituted by densely packed epithelium cells and has important structural and functional roles throughout embryonic development, morphogenesis, and adult life. Topological Defects in Epithelial Tissues adhesion (Fernandez-Gonzalez et al, 2009; Heisenberg and Bellaïche, 2013) This force generating–transmitting motor is essential for the mechanical evolution of the multicellular system, which is, most importantly, governed by a surface energy minimization principle (Lecuit and Lenne, 2007; Yu and Fernandez-Gonzalez, 2017). In order to get a more precise understanding of the not well-known mechanisms of epithelial tissue formation, computational modeling approaches have recently been applied with considerable success in recapitulating properties of epithelial structure (Farhadifar et al, 2007; Fernandez-Gonzalez and Zallen, 2008; Hocevar and Ziherl, 2009; Salbreux et al, 2012; Fletcher et al, 2013; Osterfield et al, 2013; Kachalo et al, 2015; Chen et al, 2016; Ishihara et al, 2017; Ladan et al, 2019). The common point of all modeling endeavors is the implementation of the natural tendency of cells to adopt the most stable configuration with the lowest free energy (van Drongelen et al, 2018)
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