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      Transport and self-organization across different length scales powered by motor proteins and programmed by DNA

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          Abstract

          In eukaryotic cells, cargo is transported on self-organised networks of microtubule trackways by kinesin and dynein motor proteins 1, 2 . Synthetic microtubule networks have previously been assembled in vitro 35 and microtubules have been used as shuttles to carry cargoes on lithographically-defined tracks consisting of surface-bound kinesin motors 6, 7 . Here we show that molecular signals can be used to program both the architecture and the operation of a self-organized transport system based on kinesin and microtubules and spans three orders of magnitude in length scale. A single motor protein - dimeric kinesin 1 8 - is conjugated to various DNA nanostructures to accomplish different tasks. Instructions encoded into the DNA sequences are used to direct the assembly of a polar array of microtubules and can be used to control the loading, active concentration and unloading of cargo on this track network or to trigger the disassembly of the network.

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          Most cited references30

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          Structure of a B-DNA dodecamer: conformation and dynamics.

          The crystal structure of the synthetic DNA dodecamer d(CpGpCpGpApApTpTpCpGpCpG) has been refined to a residual error of R = 17.8% at 1.9-A resolution (two-sigma data). The molecule forms slightly more than one complete turn of right-handed double-stranded B helix. The two ends of the helix overlap and interlock minor grooves with neighboring molecules up and down a 2(1) screw axis, producing a 19 degrees bend in helix axis over the 11-base-pair steps of the dodecamer. In the center of the molecule, where perturbation is least, the helix has a mean rotation of 36.9 degrees per step, or 9.8 base pairs per turn. The mean propeller twist (total dihedral angle between base planes) between A . T base pairs in the center of the molecule is 17.3 degrees, and that between C . G pairs on the two ends averages 11.5 degrees. Individual deoxyribose ring conformations as measured by the C5'-C4'-C3'-O3' torsion angle delta, exhibit an approximately Gaussian distribution centered around the C1'-exo position with delta avg = 123 degrees and a range of 79 degrees to 157 degrees. Purine sugars cluster at high delta values, and pyrimidine sugars cluster at lower delta. A tendency toward 2-fold symmetry in sugar conformation about the center of the molecule is detectable in spite of the destruction of ideal 2-fold symmetry by the molecular bending. More strikingly, sugar conformations of paired based appear to follow a "principle of anticorrelation," with delta values lying approximately the same distance to either side of the center value, delta = 123 degrees. This same anticorrelation is also observed in other DNA and DNA . RNA structures.
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            A passive pumping method for microfluidic devices.

            The surface energy present in a small drop of liquid is used to pump the liquid through a microchannel. The flow rate is determined by the volume of the drop present on the pumping port of the microchannel. A flow rate of 1.25 microL s(-1) is demonstrated using 0.5 microL drops of water. Two other fluid manipulations are demonstrated using the passive pumping method: pumping liquid to a higher gravitational potential energy and creating a plug within a microchannel.
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              Microtubule-based transport systems in neurons: the roles of kinesins and dyneins.

              The large size and extreme polarization of neurons is crucial to their ability to communicate at long distances and to form the complex cellular networks of the nervous system. The size, shape, and compartmentalization of these specialized cells must be generated and supported by the cytoskeletal systems of intracellular transport. One of the major systems is the microtubule-based transport system along which kinesin and dynein motor proteins generate force and drive the traffic of many cellular components. This review describes our current understanding of the functions of kinesins and dyneins and how these motor proteins may be harnessed to generate some of the unique properties of neuronal cells.
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                Author and article information

                Journal
                101283273
                34218
                Nat Nanotechnol
                Nat Nanotechnol
                Nature nanotechnology
                1748-3387
                1748-3395
                24 October 2013
                10 November 2013
                January 2014
                01 July 2014
                : 9
                : 1
                : 10.1038/nnano.2013.230
                Affiliations
                [1 ]University of Oxford, Department of Physics, Clarendon Laboratory, Parks Road, Oxford OX1 3PU, UK
                [2 ]Centre for Mechanochemical Cell Biology, Warwick University Medical School, Gibbet Hill, Coventry CV4 7AL, UK
                Author notes
                [*]

                Correspondence and requests for materials should be addressed to AJT.

                Author Contributions Experiments were designed by AJMW with input from CSC, HMJC, RAC and AJT. Experiments were performed by AJMW. Data was interpreted and the manuscript written by AJMW and AJT with assistance from all other authors.

                Article
                EMS55146
                10.1038/nnano.2013.230
                3883648
                24213281
                91c6a373-bce7-4173-8a3e-bfd247678994

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                Nanotechnology
                Nanotechnology

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