Developing High-Speed AFM and Nanomechanical Characterizations for Biomedical Investigations

Abstract

Atomic force microscopy (AFM) is an advanced tool that enables the visualization of dynamic behaviors and the quantification of mechanical properties under physiological conditions of biological samples from macromolecules to cells and beyond. We have constructed a high-speed AFM toward a temporal resolution of 1s or shorter using a digital versatile disc (DVD) pickup head to detect deflections from a small cantilever. In addition, a flexure-guided scanner and a sinusoidal scan method were implemented to reach 100 line/s scan rate and successful images of clathrin cages and amyloid-β fibrils in buffers. To better define nanomechanical properties of biomedical samples ranging from nanomedicine constructs to live cells and EMC-like matrices (1), we have relied on optimizing commercial AFM systems and on using force-volume and quantitative nanomechanical mapping methods. This work showcases the value of high-speed and quantitative AFM in visualizing dynamic biological behavior at nanometer scale and in defining nanomechanical properties for understanding fundamental biomedical questions. Ref (1) “Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions,” Doyle AD, Carvajal N, Jin A, Matsumoto K, and Yamada KM, Nature Commun., in press (2015).