We report the first identification of a cellular receptor mediating entry of a gram-positive bacterium into nonphagocytotic cells. By an affinity chromatography approach, we identified E-cadherin as the ligand for internalin, an L. monocytogenes protein essential for entry into epithelial cells. Expression of the chicken homolog of E-cadherin (L-CAM) in transfected fibroblasts dramatically increases entry of L. monocytogenes and promotes that of a recombinant L. innocua strain expressing internalin but does not promote entry of the wild-type noninvasive L. innocua or that of an internalin-deficient mutant of L. monocytogenes. Furthermore, L-CAM-specific antibodies block internalin-mediated entry. In contrast to Salmonella, Listeria enters cells by a mechanism of induced phagocytosis occurring without membrane ruffling. This work reveals a novel type of heterophilic interactions for E-cadherin.

The way in which cells coordinate their behaviours during various biological processes, including morphogenesis, cancer progression and tissue remodelling, largely depends on the mechanical properties of the external environment. In contrast to single cells, collective cell behaviours rely on the cellular interactions not only with the surrounding extracellular matrix but also with neighbouring cells. Collective dynamics is not simply the result of many individually moving blocks. Instead, cells coordinate their movements by actively interacting with each other. These mechanisms are governed by mechanosensitive adhesion complexes at the cell-substrate interface and cell-cell junctions, which respond to but also further transmit physical signals. The mechanosensitivity and mechanotransduction at adhesion complexes are important for regulating tissue cohesiveness and thus are important for collective cell behaviours. Recent studies have shown that the physical properties of the cellular environment, which include matrix stiffness, topography, geometry and the application of external forces, can alter collective cell behaviours, tissue organization and cell-generated forces. On the basis of these findings, we can now start building our understanding of the mechanobiology of collective cell movements that span over multiple length scales from the molecular to the tissue level.

Force sensing at cadherin-mediated adhesions is critical for their proper function. α-Catenin, which links cadherins to actomyosin, has a crucial role in this mechanosensing process. It has been hypothesized that force promotes vinculin binding, although this has never been demonstrated. X-ray structure further suggests that α-catenin adopts a stable auto-inhibitory conformation that makes the vinculin-binding site inaccessible. Here, by stretching single α-catenin molecules using magnetic tweezers, we show that the subdomains MI vinculin-binding domain (VBD) to MIII unfold in three characteristic steps: a reversible step at ~5 pN and two non-equilibrium steps at 10-15 pN. 5 pN unfolding forces trigger vinculin binding to the MI domain in a 1:1 ratio with nanomolar affinity, preventing MI domain refolding after force is released. Our findings demonstrate that physiologically relevant forces reversibly unfurl α-catenin, activating vinculin binding, which then stabilizes α-catenin in its open conformation, transforming force into a sustainable biochemical signal.