Regenerative organs, like the skin, depend on niche-stem cell interactions that sustain cellular turnover. In culture, skin fibroblasts promote epidermal stem cell proliferation and differentiation. Yet, it remains elusive how fibroblasts regulate epidermal stem cell behaviors and differentiation in vivo in skin. Here, we asked how fibroblast depletion may impact proliferation of the epidermal stem…

Cancers are complex cellular communities comprising tumor cells and their microenvironment. Recent advances in cancer biology have emerged from efforts to analyze tumors as tissues, in which emergent properties arise as tumor cells interact with one another, their microenvironment, and the host tissue. In this review, we consider interactions involving mechanical forces and mechanosignaling pathways…

Mucinous colorectal carcinoma (MUC CRC) metastasis to multiple organs, and to the peritoneum, is associated with poor prognosis. Disseminating MUC CRCs exhibit either conventional (apical-in) or inverted (apical-out) polarity that influence patient outcomes. Therefore, it is critical to identify how MUC CRC polarity is regulated. Here, we analyze patient-derived MUC CRC xenografts with either apical-in…

Nanodiscs have become an exceptionally valuable tool to explore membrane proteins in an environment resembling native membranes. However, it remains unclear how well the lipid nanodisc environment matches the conditions under which membrane proteins function in cells. The goal of this work is to use atomic-level simulations to compare the environments experienced by membrane proteins…

The blood and lymphatic vascular systems are regulated by angiopoietin (ANGPT) growth factors, which signal via endothelial TIE receptor tyrosine kinases and integrins. However, mechanistic understanding of how these receptors crosstalk is limited. Here, we show how β1-integrin inactivation regulates endothelial ANGPT/TIE2 signaling. By integrating biophysical analyses, X-ray crystallography, size-exclusion chromatography-small-angle X-ray scattering and atomistic…

Integrin adhesion complexes mediate dynamic cell-matrix interactions to regulate cell adhesion, migration and invasion. While increasing evidence suggests that adhesion components can undergo liquid-liquid phase separation, the functional relevance of adhesion-derived condensates remains elusive. Here, we demonstrate that tensin 1 (TNS1), a multidomain adaptor protein linking active integrins with the actin cytoskeleton, forms condensates in…

Capping protein (CP) regulates actin-based motility by blocking monomer exchange at the filament barbed end. Several proteins, including CARMIL, bind CP and allosterically weaken its affinity for the barbed end. CARMIL comprises pleckstrin homology (PH), leucine-rich repeat (LRR), helical dimerization (HD), CP-binding region (CBR), and proline-rich (PR) domains, but their roles in CP regulation remain…

Increased extracellular matrix deposition and stiffness promotes solid tumour progression. Yet, the precise mechanotransduction pathways, especially in less-studied mechanically responsive cancers, remain poorly understood. Here we address this gap using patient-derived tumour cells from early (mobile, T1) and advanced (immobile, T3) stages of vocal fold cancer, the most common squamous cell carcinoma severely impacting the…

The rapid, transient, and unpredictable nature of interactions between circulating cells and the endothelium challenges the investigation of these events under flow conditions. Here, we developed an imaging and image-analysis framework called FlowVision, which integrates fast, bright-field live-cell imaging with deep-learning-based image analysis to quantitatively track cell landing and arrest on an endothelial monolayer under…