Bioenergetics of cell jamming

Cellular jamming is a ubiquitous phenomenon in epithelial biology that has been shown to govern processes ranging from development in the drosophila gastrulation and zebrafish embryo vertebrate axis elongation, to disease pathophysiology including carcinoma metastasis and asthmatic airway remodeling. A jammed epithelial monolayer remains quiescent and solid-like, whereas unjamming of the monolayer leads to a solid-to-fluid transition in which the cellular collective gains a migratory phenotype, elongated cell shapes, and accompanying mechanical softening. Although jamming has been demonstrated to play a fundamental role in the dynamics of confluent epithelial tissues, the metabolic requirements that fuel the jamming transition and its associated far-from-equilibrium cellular mechanics remain unexplored. Here we measure the metabolic state of individual cells within a confluent monolayer using the cytosolic redox ratio (NAD+/NADH), a reporter of overall cellular bioenergetic potential. Surprisingly, we find that jammed cells near a PDMS barrier have a significantly increased metabolic demand. After barrier removal, and subsequent unjamming, the redox potential of cells near the leading edge of an advancing monolayer decreases to a baseline value consistent with the jammed bulk.