Maturation of the human bronchial epithelial cell (HBEC) layer causes a jamming transition, but compression of the layer, as in bronchospasm, causes unjamming

Abstract

In asthma, bronchospasm is one of major characteristics. In HBE cells in air-liquid interface (ALI) culture, compressive stress, as in bronchospasm, induces airway remodeling. Here, we investigated the physical behavior of HBE cells from normal or asthmatic donors in ALI culture. To determine an existence of jamming phase, we captured time-lapse images of HBE cells. As days progress in ALI culture, a phase transition occurred from a mobile, unjammed phase to a quiescent, jammed phase; days 6-8 in normal vs. delayed until day 14 in asthmatic cells (Fig 1). In cell lysates, the existence of vimentin was temporally well correlated with the onset of the jamming transition. In asthmatic cells during ALI days, treatment with SB431542, a TGF receptor inhibitor, promoted a jamming transition and disappearance of vimentin. Compression caused the unjamming transition of jammed cells (Fig 2), but pretreatment with SB431542 attenuated the compression-induced unjamming transition. Along with the unjamming transition, compression induced Hic-5, a LIM protein. Taken together, maturation of the HBEC layer causes a jamming transition, but compression of the layer, as in bronchospasm, causes unjamming. Importantly, TGFbeta controls this jamming transition along with vimentin and Hic-5 expression. Our findings suggest that the jamming-unjamming phase transition is a novel physical feature that captures injury-repair process and differentiates normal from asthmatic cells.