Liquid-liquid phase separation drives skin barrier formation

Abstract

Phase separation can be skin deep The skin's barrier arises from proliferative cells that generate a perpetual upward flux of terminally differentiating epidermal cells. Cells nearing the body surface suddenly lose their organelles, becoming dead cellular ghosts called squames. Working in mouse tissue, Garcia Quiroz et al. found that as differentiation-specific proteins accumulate in the keratinocytes, they undergo a vinegar-in-oil type of phase separation that crowds the cytoplasm with increasingly viscous protein droplets (see the Perspective by Rai and Pelkmans). Upon approaching the acidic skin surface, the environmentally sensitive liquid-like droplets respond and dissipate, driving squame formation. These dynamics come into play in human skin barrier diseases, where mutations cause maladapted liquid-phase transitions. Science , this issue p. eaax9554 ; see also p. 1193