DNA origami devices for molecular-scale precision measurements
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Introduction Imaging technologies such as electron microscopy and superresolution imaging, have allowed profound insights into nanoand microscale structures and mechanisms that govern many aspects of system behavior. Advances in nano- to microscale characterization (e.g., microrheology) or single-molecule experimental methods in biophysics, have led to key insights into relating component function or local material properties to system behavior. However, the capacity to manipulate and probe biological and synthetic materials systems at the nano- and microscale remains limited due to the difficulty of engineering probes with commensurate dimensions and force scales. DNA origami provides a path to construct such probes due to the ability to design precise geometry, program mechanical and dynamic properties, and incorporate chemical functionalization in a site-specific manner in devices on the scale of ∼10–1000 nm. DNA origami is uniquely suited for integration into complex materials for in situ characterization or as tools to enhance other measurement methods such as electron microscopy, atomic force microscopy (AFM), or force spectroscopy. They can also greatly enhance bulk readout methods by providing control over local parameters, such as molecular distances, within the bulk solution. Here, we summarize current applications of DNA origami nanostructures as devices for precision measurements, and we
highlight recent efforts, including implementations to enhance other imaging or measurement technologies and integration with microfabricated, synthetic, and biological materials systems.
Measurements enabled by DNA origami geometry and functionalization The ability to incorporate molecules or chemical functionalities in a site-specific manner into objects with complex geometry (see the article by Gothelf in this issue1) enables a unique level of control over templating molecules or materials at the nanoscale, which can be leveraged to develop measurement devices such as using DNA origami platforms to pattern motor proteins (proteins that use chemical energy to move along a substrate) to study their cooperative behavior 2–4 (Figure 1a) or to pattern cellular ligands to study the effects of ligand arrangement on receptor-mediated signaling5–7 (Figure 1b–c). For example, Shaw et al. used DNA origami nanocalipers to demonstrate that signal activation and invasiveness of human breast cancer cells is directly mediated by spacing of ephrin ligands presented to Eph receptors on the cell surface by testing the response of cells to ligands positioned at a variety of separation distances.7 Templating arrangements of optically active components such as fluorophores8 (Figure 1d) or gold nanoparticles9,10 (Figure 1e) enables investigating nanoscale light transport or harvesting.11
Carlos E. Castro, Department of Mechanical and Aerospace Engineering, The Ohio State University, USA; [email protected] Hendrik Dietz, Technische Universität München, Germany; [email protected] Björn Högberg, Department of Medical Biochemistry and Biophysics,
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