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Abstract: Molecular interactions govern cell behaviors. However, evolution presents us beautiful end products (e.g. molecular assemblies and machines) without a user manual, making these sophisticated systems difficult to dissect or re-engineer. Our research seeks to unlock mechanistic details of cellular organization and dynamics at the molecular level by establishing cell-free systems where the biomolecules can be precisely placed and manipulated. Specifically, we use DNA nanotechnology, an emerging technique that programs supramolecular assembly in three dimensions, to develop tools that precisely control the geometrical and mechanical attributes of artificial molecular assemblies. Here, I will share our progress on building a versatile nanoscale toolkit for high-precision membrane engineering, an adaptable framework for building nuclear pore mimics, and nanodevices to exert controlled force on mechanosensitive proteins. I will also discuss how we tackle some of the long-standing questions about biomolecular interactions using such a "DNA-guided" engineering approach.
Chenxiang Lin is an Associate Professor of Cell Biology and Biomedical Engineering at the Yale School of Medicine.