Independent Accelerator Session:
Building barriers: the power of surface condensation in epithelial sealing

Daxiao Sun

MPI of Molecular Cell Biology and Genetics, Dresden, Germany
Biotech, TU Dresden, Dresden, Germany

Epithelial tissues serve as the body’s first line of defense, with the apical junctional complex (AJC) encircling cells to mediate adhesion and barrier function. The AJC consists of tight junctions (TJs) and zonula adherens (ZAs), which, despite shared core features, transmembrane adhesion receptors and intracellular scaffolds, fulfill distinct roles in sealing and mechanical integrity. Notably, TJs and ZAs are consistently organized into vertically segregated belts, yet the mechanism driving their spatial organization and separation has remained unclear. Using a bottom-up reconstitution approach integrated with cell biology, we show that phase separation of scaffold proteins, triggered by receptor oligomerization, drives the compartmentalization of the AJC. Moreover, the size of the extracellular domains of junctional receptors governs the spatial segregation of TJ and ZA condensates by minimizing membrane bending energy. This size-dependent organization is essential for proper junctional strands assembly, actomyosin architecture, and epithelial mechanics, ultimately ensuring robust barrier function. Our findings uncover a previously unrecognized biophysical mechanism through which cells exploit intrinsic protein properties to spatially organize membrane-associated domains and direct distinct signaling outcomes. This work highlights how molecular-scale features can govern tissue-level architecture and function.

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