Currently, there is a growing need for methods that can quantify and map the molecular interactions of biological samples, both with high-force sensitivity and high spatial resolution. Force-distance (FD) curve-based atomic force microscopy is a valuable tool to simultaneously contour the surface and map the biophysical properties of biological samples at the nanoscale. We will report the use of advanced FD-based technology combined with chemically functionalized tips to probe the localization and interactions of chemical and biological sites on single native proteins and on living cells at high-resolution. I will present how an atomic force and confocal microscopy set-up allows the surface receptor landscape of cells to be imaged and the virus binding events within the first millisecond of contact with the cell to be mapped at high resolution (<50 nm). I will also highlight theoretical approaches to contour the free-energy landscape of early binding events between an engineered virus and cell surface receptors. Owing to its key capabilities (quantitative mapping, resolution of a few nanometers, and true correlation with topography), this novel biochemically sensitive imaging technique is a powerful complement to other advanced AFM modes for quantitative, high-resolution bioimaging.
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