Microfluidic device for engineering 3D epithelial monolayers with controlled pressure
Nimesh Ramesh, Integrative Cell and Tissue Dynamics
The remarkable feature of the epithelial sheets is to form specialized 3D structures suited to their physiological roles, such as highly branched structures in the lungs, drastic shape changes during embryonic development, or self-organizing organoids. These tissues are distinctive not just in the forms cells assume, but also in function. To achieve this, tissues and the cells in them exhibit coordinated behavior across the spatial and temporal scale. In a sense, 3D epithelia resemble an active material that adapts and changes in response to its biophysical-chemical stimuli like gene expression, morphogen gradients, and lumen pressure. A rheological study of the epithelia would provide unique insight on two fronts. First, to understand the fundamental physical rules of the biology, and second for inspiration of new engineering tools and design principles.
Our study focuses on the tissue response to physical forces, specifically pressure, tension, and curvature. We have fabricated a microfluidic setup to subject epithelial tissues to lumen pressure at different spatial and temporal scales. The epithelial monolayer is grown on a porous surface with circular low adhesion zones. On applying controlled pressure, the monolayer delaminates into a spherical cap (dome). Laplace law for spherical shells allows us to compute tension in the 3D structure with applied pressure and the radius of the dome.
This microfluidic device helps us to characterize the 3D epithelial shape along with the mapping of physical forces. Here, we demonstrate that the device can subject MDCK epithelial cells to a range of lumen pressure at different rates. Drastic reduction in pressure results in tissue collapsing into wrinkles; showing buckling tendency of the tissue under compression. We think that our device enables studying geometrical and biophysical constraints of tissues and unravel emergent phenomena in tissues.
Sock Shing Low, Synthetic, Perceptive, Emotive and Cognitive Systems (SPECS)
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