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Microfluidic flow of biomimetic tissues

Abstract : We designed a biomimetic prototissue as a model for cellular tissues that allows to identify the individual role of the different cellular constituents that play a role in the rheological behavior of tissues. The final goal is to characterize the flow behavior of this prototissue under microfluidic confinement. The first part of the Thesis focuses on the design and synthesis of the prototissue from the assembly of Giant Unilamellar Vesicles (GUVs). The ligand-receptor system that we used to drive the assembly was provided by the streptavidin-biotin pair. We have demonstrated that by changing the streptavidin-to-biotin ratio, the number of vesicles in solution and the biotin concentration in the vesicle membrane it is possible to tune the size of the aggregates and the compactness of the tissue. We have also been capable of changing the morphology of the biomimetic tissue from 3D-shapes to a 2D-monolayer structure by changing the incubation method. An alternative adhesion system based on DNA tethers was also evaluated. It proved to be effective in tuning the adhesion between vesicles, and was found to allow the design of prototissue with a high level of compaction. In the second part of the Thesis, the rheology of this biomimetic tissue was tested by means of a microfluidic setup. Specifically, a controlled pressure was applied and the deformation of the aggregate as it flowed through a constriction was tracked. The change in the aggregate size and shape was calculated for small aggregates, which contributed to elucidate the nature of their elastic behavior. For larger aggregates, the forward motion of the aggregate front in a microfluidic constriction as a function of time was measured. It was possible to observe a viscoelastic behavior, that we compared to the one observed in soft epithelial tissues. Both the prototissue model and the tools we developed to characterize its rheology can be implemented in the future to investigate cellular tissues mechanical properties varying its key properties: the adhesion between individual cells, the mechanical properties of the cytoskeleton and the cellular activity.
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Submitted on : Friday, June 24, 2022 - 5:46:13 PM
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Laura Casas Ferrer. Microfluidic flow of biomimetic tissues. Cristallography. Université Montpellier, 2022. English. ⟨NNT : 2022MONTS001⟩. ⟨tel-03704329⟩

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