Ratiometric Tension Probes for Mapping Receptor Forces and Clustering at Intermembrane Junctions

Short-range communication between cells is required for the survival of multicellular organisms. One mechanism of chemical signaling between adjacent cells employs surface displayed ligands and receptors that only bind when two cells make physical contact. Ligand–receptor complexes that form at the cell–cell junction and physically bridge two cells likely experience mechanical forces. A fundamental challenge in this area pertains to mapping the mechanical forces experienced by ligand–receptor complexes within such a fluid intermembrane junction. Herein, we describe the development of ratiometric tension probes for direct imaging of receptor tension, clustering, and lateral transport within a model cell–cell junction. These probes employ two fluorescent reporters that quantify both the ligand density and the ligand tension and thus generate a tension signal independent of clustering. As a proof-of-concept, we applied the ratiometric tension probes to map the forces experienced by the T-cell receptor (TCR) during activation and showed the first direct evidence that the TCR-ligand complex experiences sustained pN forces within a fluid membrane junction. We envision that the ratiometric tension probes will be broadly useful for investigating mechanotransduction in juxtacrine signaling pathways

Ratiometric Tension Probes for Mapping Receptor Forces and Clustering at Intermembrane Junctions

Short-range communication between cells is required for the survival of multicellular organisms. One mechanism of chemical signaling between adjacent cells employs surface displayed ligands and receptors that only bind when two cells make physical contact. Ligand–receptor complexes that form at the cell–cell junction and physically bridge two cells likely experience mechanical forces. A fundamental challenge in this area pertains to mapping the mechanical forces experienced by ligand–receptor complexes within such a fluid intermembrane junction. Herein, we describe the development of ratiometric tension probes for direct imaging of receptor tension, clustering, and lateral transport within a model cell–cell junction. These probes employ two fluorescent reporters that quantify both the ligand density and the ligand tension and thus generate a tension signal independent of clustering. As a proof-of-concept, we applied the ratiometric tension probes to map the forces experienced by the T-cell receptor (TCR) during activation and showed the first direct evidence that the TCR-ligand complex experiences sustained pN forces within a fluid membrane junction. We envision that the ratiometric tension probes will be broadly useful for investigating mechanotransduction in juxtacrine signaling pathways

Zinc-dependent histone deacetylases drive neutrophil extracellular trap formation and potentiate local and systemic inflammation

International audienc

The future of the global agri-food trade and the WTO

In recent years, the international trade context has seen, as a consequence of political changes, social unrest and violence, increased uncertainty and instability. Two main trends, one economic and one political, have affected the economic and political environment in which the evolution of the global trading system has been taking place.Non-PRIFPRI2MTID; LA

Light-Responsive Polymer Particles as Force Clamps for the Mechanical Unfolding of Target Molecules

Single-molecule force spectroscopy techniques are powerful tools for investigating the mechanical unfolding of biomolecules. However, they are limited in throughput and require dedicated instrumentation. Here, we report a force-generating particle that can unfold target molecules on-demand. The particle consists of a plasmonic nanorod core encapsulated with a thermoresponsive polymer shell. Optical heating of the nanorod leads to rapid collapse of the polymer, thus transducing light into mechanical work to unfold target molecules. The illumination tunes the duration and degree of particle collapse, thus controlling the lifetime and magnitude of applied forces. Single-molecule fluorescence imaging showed reproducible mechanical unfolding of DNA hairpins. We also demonstrate the triggering of 50 different particles in <1 min, exceeding the speed of conventional atomic force microscopy. The polymer force clamp represents a facile and bottom-up approach to force manipulation