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Engineering Approaches to Biomolecular Motors: From in vitro to in vivo Friday Speaker Abstracts
30
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)