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      Multidimensional Atomic Force Microscopy: A Versatile Novel Technology for Nanopharmacology Research

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          Abstract

          Nanotechnology is giving us a glimpse into a nascent field of nanopharmacology that deals with pharmacological phenomena at molecular scale. This review presents our perspective on the use of scanning probe microscopy techniques with special emphasis to multidimensional atomic force microscopy (m-AFM) to explore this new field with a particular emphasis to define targets, design therapeutics, and track outcomes of molecular-scale pharmacological interactions. The approach will be to first discuss operating principles of m-AFM and provide representative examples of studies to understand human health and disease at the molecular level and then to address different strategies in defining target macromolecules, screening potential drug candidates, developing and characterizing of drug delivery systems, and monitoring target–drug interactions. Finally, we will discuss some future directions including AFM tip-based parallel sensors integrated with other high-throughput technologies which could be a powerful platform for drug discovery.

          Electronic supplementary material

          The online version of this article (doi:10.1208/s12248-010-9232-y) contains supplementary material, which is available to authorized users.

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          Most cited references52

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          Atomic Force Microscope

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            Microfabricating conjugated polymer actuators.

            Conjugated polymer actuators can be operated in aqueous media, which makes them attractive for laboratories-on-a-chip and applications under physiological conditions. One of the most stable conjugated polymers under these conditions is polypyrrole, which can be patterned by means of standard photolithography. Polypyrrole-gold bilayer actuators that bend out of the plane of the wafer have been microfabricated in our laboratory. These can be used to move and position other microcomponents. Here we review the current status of these microactuators, outlining the methods used to fabricate them. We describe the devices that have been demonstrated as well as some potential future applications.
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              Sacrificial bonds and hidden length dissipate energy as mineralized fibrils separate during bone fracture.

              Properties of the organic matrix of bone as well as its function in the microstructure could be the key to the remarkable mechanical properties of bone. Previously, it was found that on the molecular level, calcium-mediated sacrificial bonds increased stiffness and enhanced energy dissipation in bone constituent molecules. Here we present evidence for how this sacrificial bond and hidden length mechanism contributes to the mechanical properties of the bone composite, by investigating the nanoscale arrangement of the bone constituents and their interactions. We find evidence that bone consists of mineralized collagen fibrils and a non-fibrillar organic matrix, which acts as a 'glue' that holds the mineralized fibrils together. We believe that this glue may resist the separation of mineralized collagen fibrils. As in the case of the sacrificial bonds in single molecules, the effectiveness of this mechanism increases with the presence of Ca2+ ions.
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                Author and article information

                Contributors
                +1-858-8220384 , rlal@ucsd.edu
                Journal
                AAPS J
                The AAPS Journal
                Springer US (Boston )
                1550-7416
                19 October 2010
                19 October 2010
                December 2010
                : 12
                : 4
                : 716-728
                Affiliations
                [1 ]Department of Bioengineering, University of California, San Diego, PFBH Room 219, 9500 Gilman Drive, MC 0412, La Jolla, California 92093-0412 USA
                [2 ]Department of Mechanical and Aerospace Engineering, University of California, San Diego, PFBH Room 219, 9500 Gilman Drive, MC 0412, La Jolla, California 92093-0412 USA
                [3 ]Department of Medicine, The University of Chicago, Chicago, Illinois 60637 USA
                Author notes

                Guest Editors: Rao Rapaka, Thomas Aigner, Joni Rutter, and David Shurtleff

                Article
                9232
                10.1208/s12248-010-9232-y
                2976997
                20957528
                cbf03605-96cd-4a82-ad0d-ad9156b77e96
                © The Author(s) 2010
                History
                : 25 March 2010
                : 14 September 2010
                Categories
                Mini-Review
                Custom metadata
                © American Association of Pharmaceutical Scientists 2010

                Pharmacology & Pharmaceutical medicine
                nanopharmacology,atomic force microscopy,multimodal afm,nanotherapeutics,drug discovery

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