Physical basis for the determination of lumen shape in a simple epithelium

• Published in: Nature communications Vol. 12; no. 1; p. 5608
• Main Authors: Vasquez, Claudia G., Vachharajani, Vipul T., Garzon-Coral, Carlos, Dunn, Alexander R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.09.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 14/1; 14/19; 14/35; 631/57; 631/80; 631/80/79/1987; 631/80/79/2028; 631/80/79/2066; Algorithms; Animals; Bowing; Cell culture; Cell Membrane - drug effects; Cell Membrane - metabolism; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Deamino Arginine Vasopressin - pharmacology; Dogs; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelium; Epithelium - metabolism; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Geometric constraints; Humanities and Social Sciences; Hydrostatic pressure; Kidneys; Lumens; Madin Darby Canine Kidney Cells; Microscopy; Microscopy, Confocal - methods; Models, Theoretical; multidisciplinary; Nocodazole - pharmacology; Organs; Osmosis; Osmotic pressure; Ouabain - pharmacology; Polarity; Science; Science (multidisciplinary); Spheroids; Spheroids, Cellular - cytology; Spheroids, Cellular - drug effects; Spheroids, Cellular - metabolism; Tissues; Trends; Tubulin Modulators - pharmacology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-25050-3

The formation of a hollow lumen in a formerly solid mass of cells is a key developmental process whose dysregulation leads to diseases of the kidney and other organs. Hydrostatic pressure has been proposed to drive lumen expansion, a view that is supported by experiments in the mouse blastocyst. However, lumens formed in other tissues adopt irregular shapes with cell apical faces that are bowed inward, suggesting that pressure may not be the dominant contributor to lumen shape in all cases. Here we use live-cell imaging to study the physical mechanism of lumen formation in Madin-Darby Canine Kidney cell spheroids, a canonical cell-culture model for lumenogenesis. We find that in this system, lumen shape reflects basic geometrical considerations tied to the establishment of apico-basal polarity. A physical model incorporating both cell geometry and intraluminal pressure can account for our observations as well as cases in which pressure plays a dominant role. The formation of a hollow lumen surrounded by cells is a key developmental process that sets the shape of tissues and organs. Here, the authors show how the combined influence of geometric constraints imposed by cell packing and osmotic pressure can generate the diverse range in lumen shapes observed in different tissues.