Vinculin-dependent Cadherin mechanosensing regulates efficient epithelial barrier formation.

Proper regulation of the formation and stabilization of epithelial cell-cell adhesion is crucial in embryonic morphogenesis and tissue repair processes. Defects in this process lead to organ malformation and defective epithelial barrier function. A combination of chemical and mechanical cues is used by cells to drive this process.

Quantitative imaging of epithelial cell scattering identifies specific inhibitors of cell motility and cell-cell dissociation.

The scattering of cultured epithelial cells in response to hepatocyte growth factor (HGF) is a model system that recapitulates key features of metastatic cell behavior in vitro, including disruption of cell-cell adhesions and induction of cell migration. We have developed image analysis tools that do not require fluorescence tagging and that automatically track and characterize three aspects of scattering in live cells: increase in cell motility, loss of cell-cell adhesion, and spatial dispersion of cells (the redistribution of cells during scattering). We used these tools to screen a library of drugs, and we identified several efficient inhibitors of scattering, which we classified as selective inhibitors of either motility or loss of cell-cell adhesion, or as nonselective inhibitors.

Mechanotransduction at cadherin-mediated adhesions.

Cell-to-cell junctions are crucial mechanical and signaling hubs that connect cells within tissues and probe the mechanics of the surrounding environment. Although the capacity of cell-to-extracellular-matrix (ECM) adhesions to sense matrix mechanics and proportionally modify cell functions is well established, cell-cell adhesions only recently emerged as a new class of force sensors. This finding exposes new pathways through which force can instruct cell functions.

Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner.

Cell surface receptors integrate chemical and mechanical cues to regulate a wide range of biological processes. Integrin complexes are the mechanotransducers between the extracellular matrix and the actomyosin cytoskeleton. By analogy, cadherin complexes may function as mechanosensors at cell-cell junctions, but this capacity of cadherins has not been directly demonstrated.

Selection and characterization of KDEL-specific VHH antibody fragments and their application in the study of ER resident protein expression.

Several diseases are caused by defects in the protein secretory pathway of the cell, particularly in the endoplasmic reticulum (ER). These defects are manifested by the activation of the unfolded protein response (UPR) that involves the transcriptional up-regulation of several ER resident proteins, the down-regulation of protein translation and up-regulation of ER associated degradation (ERAD). Although this transcriptional up-regulation of ER resident proteins during ER stress has been well described, data on differential protein expression of these same proteins are hardly available.