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Mechanotransduction in Cell-to-Cell Communication

Final Report Summary - MECHCOMM (Mechanotransduction in Cell-to-Cell Communication)

Cells communicate with their environment through specific interactions between ligands and receptors present in their cell membranes. These interactions are required to coordinate the activities of individual cells into functional organs and are disrupted in many diseases, including cancer. Most drugs used clinically bind to and affect the activities of membrane proteins. Therefore, it is critical for drug development to understand how membrane proteins normally relay information from the environment to the cell and how this is altered in disease. In this research project, we addressed the hypothesis that the nanoscale spatial organization of ligand/receptor interactions at the cell membrane regulates the fundamental mechanisms of action of membrane proteins.

We developed methods to control and measure the spatial organization of membrane proteins with nanoscale resolution using DNA nanotechnology. Ligand/DNA nanostructures with well-defined spatial configurations were added to live cells and we analysed how these signals were interpreted by cells. We found that the nano-organization of ligands impacted the activation of membrane receptors and ensuing intracellular responses and cellular functions in cancer and immune cells. Our findings can provide a scientific basis for the design of future nanotechnology-based biological drugs.