Towards the application of cytoskeletal motor proteins in molecular detection and diagnostic devices

Korten, Till; Månsson, Alf; Diez, Stefan

doi:10.1016/j.copbio.2010.05.001

Cited by 126 publications

(150 citation statements)

References 106 publications

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“…[50][51][52] In addition, several groups have developed models that include detailed descriptions of the single motors involved and that address specific effects such as the stochasticity of stepping 19,41,42 and the geometry of motor assemblies. 13,20,21,40 As in the experimental studies listed above, the focus of recent theoretical work has been on assemblies of two motor molecules. In particular, several recent studies have addressed the model case of two coupled kinesin-1 motors.…”

Section: Introductionmentioning

confidence: 99%

“…31,47,55 They have also provided a blueprint for the design of engineered nanoscale transport systems 26,27,40 and inspired the general theoretical study of nanoscale molecular machines. 47 Our current understanding of how these molecular motors work has been advanced greatly by the use of single molecule technology such as optical tweezers, 58 which allowed for the quantitative characterization of the motor's behavior under the influence of external force.…”

Section: Introductionmentioning

confidence: 99%

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Elastic Coupling Effects in Cooperative Transport by a Pair of Molecular Motors

et al. 2012

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Abstract-Engineered constructs coupling a defined number of molecular motors provide an opportunity to study the cooperative transport of cargoes. Theoretical descriptions for the dynamics of such complexes can help to understand experimental data or to quantitatively formulate expectations for such experiments and provide a general framework for such analysis. Here, we review and extend recent theoretical studies that focused on pairs of molecular motors to study effects of coupling between the motors. We derive explicit results for two elastically coupled kinesin-1 motors as a function of the coupling strength using both linear and nonlinear springs. In addition, we discuss the general dynamics of such motor pairs, which is governed by characteristic time scales for the spontaneous unbinding of motors and for the built-up of strain forces that are sufficiently large to affect the run length and/or the velocity of the motors. We show how the comparison of these time scales can be used to predict the distinct behavior of different motor species, the effects of coupling, and the impact of the single motor velocity on the observable dynamics of a motor pair.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elastic Coupling Effects in Cooperative Transport by a Pair of Molecular Motors

et al. 2012

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“… Engineering biomolecular motors can provide direct tests of structure-function relationships and customized components for controlling molecular transport in artificial systems 1 or in living cells 2 . Previously, synthetic nucleic acid motors 3–5 and modified natural protein motors 6–10 have been developed in separate complementary strategies for achieving tunable and controllable motor function.…”

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confidence: 99%

“…Replacing protein structural elements with nucleic acids allows for versatile design using easily controlled duplex lengths and a repertoire of modular RNA structural elements 33 , and hybrid motors may in future be integrated with RNA 34 or DNA 35 origami platforms to produce large functional assemblies with defined motor orientations, as seen in some biological motor assemblies such as myosin filaments 15,18 . Applications of hybrid motors may include artificial molecular transport systems in programmable devices 1 , where the designs described here provide the possibility of using DNA computational outputs 21 to control the directions and speeds of sequence-addressable populations of biologically derived protein motors. Switch strands bind to the motor and thus function as both signals and cargos, which may be exploited in artificial transport systems; for example, a bidirectional shuttle that reverses direction after dropping off a cargo may be implemented by conjugating the switch strand to a cargo molecule and affixing the switchback strand to a dropoff site.…”

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confidence: 99%

Controllable molecular motors engineered from myosin and RNA

et al. 2017

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Engineering biomolecular motors can provide direct tests of structure-function relationships and customized components for controlling molecular transport in artificial systems1 or in living cells2. Previously, synthetic nucleic acid motors3–5 and modified natural protein motors6–10 have been developed in separate complementary strategies for achieving tunable and controllable motor function. Integrating protein and nucleic acid components to form engineered nucleoprotein motors may enable additional sophisticated functionalities. However, this potential has only begun to be explored in pioneering work harnessing DNA scaffolds to dictate the spacing, number, and composition of tethered protein motors11–15. Here, we describe myosin motors that incorporate RNA lever arms, forming hybrid assemblies in which conformational changes in the protein motor domain are amplified and redirected by nucleic acid structures. The RNA lever arm geometry determines the speed and direction of motor transport, and can be dynamically controlled using programmed transitions in lever arm structure7,9. We have characterized the hybrid motors using in vitro motility assays, single-molecule tracking, cryo-electron microscopy, and structural probing16. Our designs include nucleoprotein motors that reversibly change direction in response to oligonucleotides that drive strand-displacement17 reactions. In multimeric assemblies, the controllable motors walk processively along actin filaments at speeds of 10–20 nm s−1. Finally, to illustrate the potential for multiplexed addressable control, we demonstrate sequence-specific responses of RNA variants to oligonucleotide signals.

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“…Currently, the in vitro motility assay is also used to determine the feasibility of constructing motor protein-based artificial biomachines, for which actin-myosin or MT-kinesin systems are considered promising building blocks. [8][9][10][11][12][13][14][15][16] New classes of devices including nanoscale molecular shuttles, 17,18 surface-imaging processes, 19 force measurements 20 and lab-on-a-chip devices 21 have been developed using knowledge obtained through the in vitro motility assay. To improve the organizational hierarchy of motor protein-based systems with emergent functions similar to those observed in natural systems, several active self-organization (AcSO) techniques have been developed.…”

Section: Introductionmentioning

confidence: 99%

Active self-organization of microtubules in an inert chamber system

Kabir

Inoue

Kakugo

et al. 2012

Polym J

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Microtubule-kinesin system is considered as a building block for the construction of artificial biomachines, and active selforganization of microtubules has been used to integrate their structural organization and achieve amplified functions similar to those observed in natural systems. However, the short lifetime of assembled structures has limited their use in organized systems. In the present study, we demonstrated that the use of an inert atmosphere in the self-organization of microtubules allows the assembled structures to remain active for a prolonged period of time (10 times longer). The longer lifetime achieved in the present study will facilitate the development of assembled microtubules for designing biomolecular motor-based efficient artificial biomachines with prolonged lifetimes. Polymer Journal ( Keywords: active self-organization; biomachine; biomolecular motor; kinesin; lifetime; microtubule INTRODUCTION Actin-myosin and microtubule (MT)-kinesin systems are known for their fascinating in vivo activities with respect to cell motility, 1 cytokinesis 2 and cellular transport. To unveil the functions of bimolecular motor systems 3-5 and to elucidate the in vivo mechanism of actin-myosin or MT-kinesin interactions, in vitro motility assay 6,7 has been used over the last few decades. Currently, the in vitro motility assay is also used to determine the feasibility of constructing motor protein-based artificial biomachines, for which actin-myosin or MT-kinesin systems are considered promising building blocks. [8][9][10][11][12][13][14][15][16] New classes of devices including nanoscale molecular shuttles, 17,18 surface-imaging processes, 19 force measurements 20 and lab-on-a-chip devices 21 have been developed using knowledge obtained through the in vitro motility assay. To improve the organizational hierarchy of motor protein-based systems with emergent functions similar to those observed in natural systems, several active self-organization (AcSO) techniques have been developed. [22][23][24][25] For instance, a specific streptavidin (St)-biotin (Bt) interaction has been used in the in vitro motility assay of MTs on a kinesin-fixed surface, and a variety of well-organized MTs assemblies have been produced including linear bundles, rings and network structures, all of which showed motility comparable to that of single MT filaments. However, the lifetime of biomolecular motors is short owing to the attack of reactive oxygen species (ROS), which terminates their activity and limits the long-term utilization of assembled structures. Thus, assembled structures formed under ambient aerobic conditions remain active for only B90 min.

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Towards the application of cytoskeletal motor proteins in molecular detection and diagnostic devices

Cited by 126 publications

References 106 publications

Elastic Coupling Effects in Cooperative Transport by a Pair of Molecular Motors

Elastic Coupling Effects in Cooperative Transport by a Pair of Molecular Motors

Controllable molecular motors engineered from myosin and RNA

Active self-organization of microtubules in an inert chamber system

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