Tight junction mechanics
Tight junctions are are well known to be important determinant of epithelial barrier function, however, recent studies have also revealed that they can sense and regulate apical forces. Classically tight junctions seal the intercellular spaces between adjacent epithelial cells and form regulated, selective (size- and ion-specific) barriers. Barrier function can be acutely regulated in epithelial tissues by signaling mechanisms – notably by changes in actomyosin contractility \cite{Shen2011}. To achieve these functions, the tight junction transmembrane proteins (Claudins, Occludin, immunoglobulin-like JAMs) form tight junction strands, which are linked to the underlying actomyosin cytoskeleton via cytoplasmic plaque proteins (Zonula Occludens (ZO) proteins, Cingulin, Afadin, etc.) \cite{Van2014} (Fig qq). The ZO proteins (ZO-1, ZO-2, and ZO-3) bind to the cytoplasmic tail of Claudins and Occludin with their N-termini \cite{Itoh1999,Li2005}. ZO-1 interacts with F-actin through its C-terminus; ZO-2 and ZO-3 also interact with F-actin, although the binding sites have not been determined \cite{Fanning1998,Wittchen1999}. ZO proteins are proposed to initiate the polymerization of Claudins into TJ strands \cite{Umeda2006}, and ZO-1 has the ability to stabilize Claudin strands \cite{27974639}. In addition to their role in regulating the barrier of epithelial sheets it is also becoming clear that tight junctions are also important regulators of epithelial mechanics. For example, when ZO-1 and -2 are depleted F-actin and Myosin II dramatically increase at adherens junctions and generate high tension in line with the junction \cite{Fanning2012,Choi2016} meaning tight junction negatively regulate tension on adherens junctions \cite{Hatte2018}. Additional work has shown that ZO-1 itself is mechanosensitive. Tensile force along ZO-1 reveals a binding site for the transcription factor DbpA, thus sequestering it to inhibit cell proliferation, with additional possible effects on barrier function and epithelial morphogenesis \cite{Spadaro2017}. These initial studies position tight junctions as important mechanical signaling centers in addition to the classic role in regulating tissue barrier function.