Research Projects

The morphology of the tissue growth and organ development is predominantly governed by mechanical cues in the tissue and the surroundings, and their cellular interactions with the environment. The experimental observations evidently describe the fact that the mechanical forces and geometry efficiently coordinate cell behaviour and ECM through feedback and mechanical homeostasis, leading to emergent properties which are not directly evident from the behaviour of individual cells. Earlier, the focus of the most studies has been to understand the importance of chemical morphogen gradients in the development but with time it is becoming more and more clear that mechanical cues in the tissue and the surrounding 3D ECM also control tissue organization and morphogenesis. The role of elasticity in tissue growth and morphogenesis has been studied extensively whereas the exploration of the role of viscosity versus elasticity of the matrix in the tissue response has just begun. Recently we studied the effect of viscoelastic properties of passive extracellular matrix on breast epithelial cells in both computational and experimental frameworks. We have found matrix viscoelasticity prompts the spheroidal tissue to break symmetry which leads to invasive finger like pattern of the spheroid. Aforementioned study considers that the ECM is homogeneous, whereas in vivo the ECM can be heterogeneous and also the growing tissue may degrade the ECM. Now we would like to extend this by designing an ECM with heterogeneous mechanical property and explore how the tissue growth and invasive finger formation can get affected. The next step would be to design the matrix that is degrading when it is in contact with the tissues and how the magnitude of degradation can affect the tissue organization and invasive finger formation. This is a similar phenomenon that is seen in the tumorogenesis, where matrix metalloproteinases (MMP) secretions is profound leading to ECM degradation. At IITH we will be developing the mathematical model and computational methods using an agent-based model (ABM) and a continuum model. This has been described in detail in the methodology section. Using ABM, we have already shown that by controlling the degree of viscoelasticity we can have qualitatively different growth and morphology of the tissue. We have also designed a heterogeneous matrix and preliminary results show that the persistent invasive fingers are guided by the regions of low viscosity. This needs a detailed investigation. The next step in ABM would be to show that matrix degradation can regulate tissue organization and morphogenesis. For the continuum model, we are developing the model and for the Newtonian two-phase case, we show that the activity of the fluid, which is directly related to tissue growth and cell level motility, controls the morphology of the growing tissue which is very different from the classical counterpart that is Saffman-Taylor viscous fingering.

Development Biophysics, Computational Biology, Tissue Organization, Non-equilibrium systems, Active Matter