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Mechanotransduction in Cell-to-Cell Communication

Periodic Report Summary 2 - MECHCOMM (Mechanotransduction in Cell-to-Cell Communication)

Cells communicate with adjacent cells through specific interactions between ligand and receptor proteins present in their respective cell membranes. These interactions are required to coordinate cellular activities to form functional organs and are disrupted in many diseases, including cancer. The majority of drugs currently in clinical use bind and affect the activity of membrane proteins. Therefore, it is critical for drug development to understand how membrane proteins function and how they relay information from the environment to the cell. In this research program, we address the hypothesis that the physical context of the ligand/receptor interactions contributes to defining their fundamental mechanisms of action in cell-to-cell communication.

We have developed methods to control the spatial distribution and lateral mobility of ligands so that we can study the effects of these variables on the functions of membrane receptors. We combine DNA scaffolds with proteins to form spatial patterns of ligands of nanoscale dimensions. These ligand nanostructures are added to live cells and we analyze how these signals are interpreted by cells. We found that the spatial distribution of ligands regulates the levels of receptor activation as well as the RNA content of cells. This work aims to provide a scientific basis for the development of new types of drugs that modulate the physical context of the ligand/receptor interaction and its functional consequences.