General overview
Epithelial tissues show interesting physical properties such as glassiness and the associated dynamic heterogeneity. Unlike other passive glasses, epithelia are active. Does biological activity alter glassy dynamics in epithelia? On the other hand, does the physical glassiness of the tissue, and the associated movement patterns, affect its biological properties such as protein expression?
To answer these questions, I am studying the spatiotemporal dynamics of forces and mechanotransducer proteins in epithelia using experimental techniques such as high-resolution timelapse imaging, traction force microscopy, monolayer stress micorscopy and immunostaining. We then analyse the experimental data by image processing, cell segmentation and tracking, Particle Image velocimetry, Bayesian force inference etc.
Firstly, we answered the question on how epithelia can show glassy dynamics in the first place, since activity should theoretically fluidise the tissue- you can find more details here and the preprint here. We find that both mechanochamical feedback and crowding are required for the emergence of glassy dynamics in active epithelia.
However, even crowded epithelia can sometimes fluidise, which we have investigated in this project.
Now, we are also exploring the role of spatiotemporal dynamics of proteins and forces in epithelia in epithelial tissue functions such as the extrusion of transformed cells (Epithelial Defense Against Cancer- EDAC) and wound healing. Besides these, I have also been involved in other collaborative projects within and outside the lab.
Below, I have tried to explain some of the above concepts without jargon to make my work accessible to non-specialists:
EPITHELIAL TISSUES
Epithelial tissues such as the skin, cover and protect our organs.
They are sheet-like with tightly packed cells, forming a physical barrier.
Mechanical forces in epithelia
Epithelial cells are connected to each other like holding hands. So, they can push and pull each other. We call this cell-cell forces.
They grow on top of a jelly-like substance called the ECM. They attach to the ECM and apply force on it to move. Like how we apply a backward force with our foot to move forward. We call this Traction.
Biochemical heterogeneity
Different cells of the tissue also have different protein levels- We call this biochemical heterogeneity.
This may be due to cell intrinsic noise in gene expression levels etc, or cell-extrinsic sources of noise such as asynchronous cell cycles.
Glassy dynamics
Usually, when a liquid is cooled slowly, its molecules have enough time to arrange themselves into an orderly, repeating pattern—this forms a crystalline solid, like ice or salt.
But if it is rapidly cooled, the molecules don’t get enough time to organize themselves properly. So, they form a glassy state which is an intermediate state between solids and liquids.
In glassy materials, the molecules are packed tightly. Because they’re so close together, each one is “caged in” by its neighbors, and they move with highly correlated velocitites.
This creates mesoscale regions of highly correlated velocities that may be fast or slow, called Dynamic heterogeneity.