RT Journal Article
SR Electronic
T1 A geometry-based model describes lumen stability in epithelial cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 746792
DO 10.1101/746792
A1 Claudia G. Vasquez
A1 Vipul T. Vachharajani
A1 Carlos Garzon-Coral
A1 Alexander R. Dunn
YR 2019
UL http://biorxiv.org/content/early/2019/08/28/746792.abstract
AB 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. While prior work has described the hydrostatic pressure-driven expansion of lumens when they are large, the physical mechanisms that promote the formation and maintenance of small, nascent lumens are less explored. In particular, models that rely solely on pressure-driven expansion face a potential challenge in that the Laplace pressure, which resists lumen expansion, is predicted to scale inversely with lumen radius. We investigated the cellular and physical mechanisms responsible for stabilizing the initial stages of lumen growth using a 3D culture system in which epithelial cells spontaneously form hollow lumens. Our experiments revealed that neither the actomyosin nor microtubule cytoskeletons are required to stabilize lumen geometry, and that a positive intraluminal pressure is not necessary for lumen stability. Instead, our observations are in agreement with a quantitative model in which cells maintain lumen shape due to topological and geometrical factors tied to the establishment of apico-basolateral polarity. We suggest that this model may provide a general physical mechanism for the formation of luminal openings in a variety of physiological contexts.