Lakshmi BALASUBRAMANIAM

Role of E-cadherin in altering tissue topology during collective migration
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Cellular tissues are adaptable and robust, having the collective ability to respond to mechanical stresses. Tissue homeostasis relies on a tight balance between cell proliferation and cell extrusion. We recently found that cell extrusion mechanisms are related to local misalignments of cells and increased compressive stress (Saw et al Nature). Defects are locations of high stress thereby expelling cells out of the cell monolayer either through the contraction of acto-myosin cable or lamellipodia formation (Kocgozlu Curr Biol) and these cellular misalignments, also known as topological defects, can be understood in the framework of the physics of active nematic liquid crystals. In addition, the understanding of cellular extrusion mechanisms in epithelial cells shows that epithelial cells display particular properties. They behave as an extensible nematic system whereas a confluent layer of fibroblast collectively has been shown to behave as a contractile system (Silberzan Nature Phys). Since these cell lines express different kinds of cadherin-based junctions which vary the stability and strength, we anticipate that cadherin-based junctions can dictate the behavior of cellular tissues. Using an in vitro assay of MDCK cells, we are study the role of adherens junctions in directing contractile vs extensile behavior during collective migration of cells thereby enabling us to link tissue topology and fate of a cell. This difference in the active behavior of the cell monolayers could shed some light into the role played by cadherins and more generally intercellular junctions during tissue homeostasis.