Executive Summary : | A tissue is a group of cells with a similar structure and function, in close proximity, organized to perform one or more specific functions. The process by which a tissue develops its shape is described as tissue morphogenesis. Tissue morphogenesis typically involves changes in the cell number, shape, size, and position. These changes at the cellular level, either independently or together are responsible for tissue self-organization. The properties of the cells at the individual level can also get affected by the environment it thrives in, i.e., the mechanical properties of the extra cellular matrix (ECM). ECM provides mechanical support and anchorage for the cell that helps it to maintain its shape and growth in addition to cell polarity, cell differentiation, cell adhesion, cell migration thereby regulating growth mechanism, regeneration and healing process. Thus, there is a compelling need to understand how such physical forces are generated at an individual cellular level and transmitted to adjoining cells affecting tissue morphogenesis. These questions will be addressed by changing the two parameters: (a) mechanical property of the ECM and (b) Cell type, one at a time. We are planning to do both experimental and computational work. The experiments will be performed by our collaborator Dr. Alberto Elosegui-Artola at Francis-Crick Institute. London, UK; whereas the computational model will be done by my group at IITH. I will take insights from the experiments and develop the computational model to recapitulate these observations and explain how by changing the forces of cell-cell interaction, cell-ECM interaction, cell proliferation, cell apoptosis, and cell motility can affect tissue morphogenesis. I will develop two computational approaches, one at the microscopic cellular level and the other at the macroscopic level to understand tissue morphogenesis. In the microscopic model, the individual cells in the tissue are modeled as overdamped soft elastic spheres of size in a liquid of effective viscosity, which move under the influence of three forces: (i) the interaction between cells, (ii) the repulsion between the cell and the surrounding viscoelastic matrix (modeled as a set of similar spheres of size), and (iii) the activity of cells. In the macroscopic model, the tissue is modeled as a circular droplet of a growing active fluid, with an unperturbed, time-dependent radius. The surrounding ECM is modeled as a passive, viscoelastic fluid. I will use the Cahn-Hilliard equation to mimic the two-phase system. Since the viscous forces are dominant in this limit, I will use the stokes equation to mimic flow with an active term that is proportional to the flow velocity, this equation will be coupled by the Cahn-Hilliard equation. By modifying the mass balance equation, we can control cell proliferation and cell apoptosis. To bring in the viscoelasticity, I will couple the stokes equation with the FENE-P equation. |