Research Projects

Cell migration plays an important role in many biological processes, such as tumor invasion, cancer metastasis, immune responses etc. Various in-vitro experiments are carried out to understand the migration properties of a cell at the individual level. The migration behavior of cells are largely determined by the surface topography. For example, Dictyostelium discoideum cells prefer to migrate along the circumferential direction on a cylindrical fiber or a micropillar, while MDCK cells have a tendency to migrate along the axis inside a tube. The direction of migration of different cell types (T-cells, D. d cells, Keratocytes etc.) on sinusoidal wavy patterns are found to depend upon the ratio of cell size to the wavelength of the sinusoidal patterns [R K Sadhu at al. PNAS 2024]. Recently we have proposed a theoretical model where a lamellipodia-like structure forms as a self-organization of curved actin nucleators on a vesicle, coupled with adhesion to the substrate [R K Sadhu at al., Nat. Comm 2023, PNAS 2024]. This model captures the experimental observations discussed above and shows that migrating cells exhibit some universal feature that are not cell-type specific. A cell in vivo is not isolated, rather it is surrounded by many other cells, tissues or organs, and it interacts continuously with the soft extracellular matrices. The shape and migration behaviour of cell collections are different from a single cell, as for cell collections, the shape and migration properties will also be affected by cell-cell interaction as well as on collective effects. For example, a single cell prefers to migrate circumferentially when exposed to a cylindrical fiber (convex shape), and axially when placed inside a tube (concave shape) [R K Sadhu at al. PNAS 2024], while an epithelial monolayer is reported to migrate circumferentially in both kinds of curvatures [Alexandros Glentis et. al, Science advances, 2022]. However, how a collection of cells behave differently than a single cell when exposed to different kinds of substrate curvatures are not well understood. Cells in vivo migrate over soft extracellular matrices, over another cell or tissue that are non-rigid. The mechanical properties of these cellular environment also play a major role in the regulation of cell spreading and migration. How the substrate mechanical properties, such as its stiffness, affect the migration behavior of cell collections are also not well understood at present. I plan to extend our previous theoretical model to study the migration of cell collection on a substrate of different geometrical and mechanical properties. The study will allow us to understand how collection of cells behave when exposed to curvature cues, and also allow us to explain several in vitro experiments carried out by many researchers. The study will also reveal how a collection of cells behaves when it migrates on a substrate of varying stiffness, such as inside our body.