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Qingzong Tseng

Study of multicellular architecture with controlled microenvironment

Published on 1 July 2011

Thesis presented July 01, 2011

This thesis dissertation is comprised of three major parts. The first part devotes to  all the technological developments that have been realized in my thesis study. These developments in microfabrication, in image acquisition and analysis, and in the traction force analysis had solved various problems we have encountered during our study of epithelial architecture.
The second part describes the study of the spatial organization of the adhesion systems in epithelia. From their polarity, their functioning, to their remodeling, the epithelial architecture is deeply linked with the adhesion systems. With the capability to well defin​e the location of cell-matrix interaction, we examined how the intercellular adhesion was organized according to the cell-matrix adhesion. Our results highlighted the instructive role of cell-matrix adhesion in organizing the intercellular adhesion. This organization subsequently governed the internal polarity which was indicated by the centrosome positioning. During epithelial remodeling, both the adhesion system and internal polarity were subjected to modification. Nevertheless they could be regulated differently depending on the context of remodeling.
The last part is focused on the physical aspect of the epithelial architecture. Apart from the biochemical signaling network, mechanical force is also a substantial ingredient in morphogenesis. Together with our techniques in micropatterning the soft gel, the development of software for traction force microscope, and our knowledge of cell-cell positioning, we were able to analyze precisely the mechanical property of the multicellular architecture. We found that the cellular contractility was modulated by the spatial organization of the adhesion system. It permitted us to complete the current physical model of epithelial geometry with an anisotropic term for contractility. This new physical model could effectively account for the cell positioning on various matrix geometries.

Micropattern, morphogenesis, image analysis, traction force, microscopy, cytoskeleton, polarity

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