Physical basis of lumen shape and stability in a simple epithelium

Abstract

A continuous sheet of epithelial cells surrounding a hollow opening, or lumen, defines the basic topology of numerous organs. De novo lumen formation is a central feature of embryonic development whose dysregulation leads to congenital and acquired diseases of the kidney and other organs. Hydrostatic pressure has been proposed to drive lumen expansion, a view that is supported by recent experiments in the mouse blastocyst. High luminal pressure should produce lumen surfaces that bow outwards toward the surrounding cells. However, lumens formed in other embryonic tissues adopt highly irregular shapes, with cell apical faces that are bowed inward, suggesting that pressure may not be the dominant contributor to lumen growth in all cases. We used three-dimensional live-cell imaging to study the physical mechanism of lumen formation in Madin Darby Canine Kidney (MDCK) cell spheroids, a canonical cell-culture model for lumenogenesis. Our experiments revealed that neither lumen pressure nor the actomyosin cytoskeleton were required to maintain lumen shape or stability. Instead, we find that, in our model system, lumen shape results from simple geometrical factors tied to the establishment of apico-basal polarity. A quantitative physical model that incorporates cell geometry, cortical tension, and intraluminal pressure can account for our observations as well as cases in which pressure indeed plays a dominant role. Our results thus support a unifying physical mechanism for the formation of luminal openings in a variety of physiological contexts.