Abstract
The healthy and mature epithelial layer is ordinarily quiescent, non-migratory, solid-like, and jammed. However, in a variety of circumstances the layer transitions to a phase that is dynamic, migratory, fluid-like and unjammed. This has been demonstrated in the developing embryo, the developing avian airway, the epithelial layer reconstituted in vitro from asthmatic donors, wounding, and exposure to mechanical stress. Here we examine the extent to which ionizing radiation might similarly provoke epithelial layer unjamming. We exposed primary human bronchial epithelial (HBE) cells maintained in air-liquid interface (ALI) to sub-therapeutic doses (1 Gy) of ionizing radiation (IR). We first assessed: (1) DNA damage by measuring p-H2AX, (2) the integrity of the epithelial layer by measuring transepithelial electrical resistance (TEER), and (3) the extent of epithelial cell differentiation by detecting markers of differentiated airway epithelial cells. As expected, IR exposure induced DNA damage but, surprisingly, disrupted neither normal differentiation nor the integrity of the epithelial cell layer. We then measured cell shape and cellular migration to determine the extent of the unjamming transition (UJT). IR caused cell shape elongation and increased cellular motility, both of which are hallmarks of the UJT as previously confirmed. To understand the mechanism of IR-induced UJT, we inhibited TGF-β receptor activity, and found that migratory responses were attenuated. Together, these observations show that IR can provoke epithelial layer unjamming in a TGF-β receptor-dependent manner.
Highlights
The healthy and mature epithelial layer is ordinarily quiescent, non-migratory, solid-like, and jammed
Air-liquid interface (ALI) culture recapitulates the environment in which bronchial epithelial cells exist within the airway in vivo
Using primary human bronchial epithelial (HBE) cells maintained in air-liquid interface (ALI), we examined the effects of irradiation on the homeostatic function of epithelial cells, as well as cellular migration
Summary
The healthy and mature epithelial layer is ordinarily quiescent, non-migratory, solid-like, and jammed. Epithelial cells become elongated in shape and rearrange cooperatively with their neighbors (Sadati et al, 2013; Fredberg, 2014; Park et al, 2015, 2016; Pegoraro et al, 2016; Atia et al, 2018) This phase transition from the jammed to the unjammed phase, called the unjamming transition (UJT), was discovered in a living system using well-differentiated human bronchial epithelial (HBE) cells exposed to mechanical compression that mimics the mechanical effect of bronchospasm (Park et al, 2015). Since this discovery of these dynamic and structural hallmarks of epithelial UJT (Park et al, 2015; Atia et al, 2018), work from our team and others
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