Hydraulic forces generated from active fluid pumping are important in tissue morphogenesis and homeostasis, and could also underlie multiple morphogenic events seen in other developmental contexts. When a stall pressure is reached, the fluid flux vanishes. For the kidney, it was shown that tubular epithelial cells behave as active mechanical fluid pumps: the trans-epithelial fluid flux depends on the hydraulic pressure difference across the epithelial layer. Recently, the trans-epithelial fluid flux and the hydraulic pressure gradient have been explicitly measured for a variety of cellular and tissue model systems across various species. The basic physics of this process is described by the osmotic engine model, which also underlies actin-independent cell migration. Cells use directional transport of ions and osmotic gradients to drive fluid flow across the cell surface, in the process also building up fluid pressure. Finally, we show that the model successfully predicts normal lumen morphogenesis when the matrix density is physiological and aberrant multilumen formation when the matrix density is excessive.Īctive fluid transport across epithelial monolayers is emerging as a major driving force of tissue morphogenesis in a variety of healthy and diseased systems, as well as during embryonic development. Then, we study the formation of the lumen under different-mechanical scenarios and conclude that an increase in the matrix density reduces the lumen volume and hinders lumen morphogenesis. Moreover, this computer-based model considers the variation in the biological behavior of cells in response to the mechanical forces that they sense. For this purpose, we develop a 3D agent-based-model for lumen morphogenesis that includes cells’ fluid secretion and the density of the extracellular matrix. In particular, we consider the hydrostatic pressure generated by the cells’ fluid secretion as the driving force and the density of the extracellular matrix as regulators of the process. Here, we focus on the development of a mechanistic model for computationally simulating lumen morphogenesis. However, how these factors coordinate is not yet fully understood.
The correct function of many organs depends on proper lumen morphogenesis, which requires the orchestration of both biological and mechanical aspects.
We study the lumen growth dynamics resulting from the balance between (i) the active and passive ion trans- port across membranes both in the lumen and in the cleft, (ii) the passive transport of water along transmembrane osmotic and hydrostatic gradients, (iii) the paracellular leakage. All results are in the scaled units of the model (see SI Appendix, Table S1) as well as in "international units" based on the estimations derived in SI Appendix, SI(2). We estab- lished the expressions of the conservation laws in the lumen and in the cleft accounting for this geometry. As the lumen develops, the dimensions of the spherical caps vary, but the cell contact remains fixed with a total size L. The remaining paracellular adhesive cleft has a thickness e. The lumen elongates parallel to the cell-cell contact over a distance r l and its apex height is h. 2) with a radius of curvature R and a contact angle ✓ at the lumen edge. consider the lumen as two symmetrical contractile spher- ical caps ( Fig.
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