Engineering Approaches to Biomolecular Motors

Engineering Approaches to Biomolecular Motors: From in vitro to in vivo Friday Speaker Abstracts

Chemomechanical Models for the Rational Design and Studies of Engineered Molecular Motors Alf Månsson Linnaeus University, Kalmar, Sweden. Molecular motors and cytoskeletal filaments may be genetically and/or chemically engineered for external modulation and controlled switching of their properties, e.g. the direction of filament transport by the motors. In addition to forming the basis for entirely new nanotechnological applications, such engineering opens for functional insights beyond those obtainable in conventional biophysical studies. In order to aid insights and design, a new chemomechanical modelling approach is here reported that connects kinetic and elastic properties of the motors with observable variables such as force, velocity and direction of motion of motor propelled filaments (1). The model performance is illustrated by Monte-Carlo simulations of force-, and motion-generation by the actin-myosin motor system of muscle. Using independent parameter values from published data, it is shown that a given model accounts well for experimental observations of force-, and motion-generation from single molecules to the large motor ensembles of muscle. It is further demonstrated how the model may be modified to simulate changes in actin-myosin function achievable by genetic or chemical engineering. This includes changes in kinetics or motor elasticity with effects on sliding velocity and/or processivity as well as changed power-stroke direction with altered transportation direction. Finally, a strategy is described for combining modelling of motor properties with simulation of filament elasticity and prediction of motor propelled filament paths on flat, as well as nanostructured surfaces. To conclude, it is shown that one given model accounts for the function of muscle actomyosin from single molecules to the large ensembles in muscle cells. Furthermore, the usefulness of this model in aiding design and studies of engineered myosins is demonstrated. (1) Mansson, A. (2010). Biophys. J. 98:1237-1246. Supported by the FET-program of EU-FP7 (grant agreement 613044; ABACUS)

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