Abstract
Molecular motor gliding motility assays based on myosin/actin or kinesin/microtubules are of interest for nanotechnology applications ranging from cargo-trafficking in lab-on-a-chip devices to novel biocomputation strategies. Prototype systems are typically monitored by expensive and bulky fluorescence microscopy systems. The development of integrated, direct electric detection of single filaments would strongly benefit applications and scale-up. We present estimates for the viability of such a detector by calculating the electrostatic potential change generated at a carbon nanotube transistor by a motile actin filament or microtubule under realistic gliding assay conditions. We combine this with detection limits based on previous state-of-the-art experiments using carbon nanotube transistors to detect catalysis by a bound lysozyme molecule and melting of a bound short-strand DNA molecule. Our results show that detection should be possible for both actin and microtubules using existing low ionic strength buffers given good device design, e.g., by raising the transistor slightly above the guiding channel floor. We perform studies as a function of buffer ionic strength, height of the transistor above the guiding channel floor, presence/absence of the casein surface passivation layer for microtubule assays and the linear charge density of the actin filaments/microtubules. We show that detection of microtubules is a more likely prospect given their smaller height of travel above the surface, higher negative charge density and the casein passivation, and may possibly be achieved with the nanoscale transistor sitting directly on the guiding channel floor.
Highlights
A key frontier in nanotechnology in recent decades has been the development of functional nanodevices featuring biomolecular motors, with a strong focus on motile ‘gliding’ assays using the actin-myosin and kinesin-microtubule molecular motor systems [1, 2, 3, 4]
With a basic device concept sketched out, we focus entirely for the remainder of this work on Prospects for single-molecule electrostatic detection in molecular motor gliding motility assays4
We work from published experiments, in particular, Choi et al [27] and Sorgenfrei et al [26] to establish the limits of detection for a change in electric potential at a nanotube transistor due to a biological target, e.g., Prospects for single-molecule electrostatic detection in molecular motor gliding motility assays5 lysozyme catalysis and DNA melting, respectively
Summary
A key frontier in nanotechnology in recent decades has been the development of functional nanodevices featuring biomolecular motors, with a strong focus on motile ‘gliding’ assays using the actin-myosin and kinesin-microtubule molecular motor systems [1, 2, 3, 4]. Network-based biocomputation [16] is a strong motivator to extend beyond microscope-based detection of filaments because scale-up inevitably leads to the need to detect filament passage at a very large number of points spread across an area much larger than the field-of-view for an appropriate magnification objective This need for new detection strategies led us to consider an electrical approach where a nanoscale transistor made with, e.g., carbon nanotubes, graphene or semiconductor nanowires, spans the bottom of a lithographically-patterned guiding structure. Both actin filaments [19] and microtubules [20] carry negative charge that can in principle electrostatically gate a nanoscale transistor providing it passes within a distance smaller than the buffer’s Debye length. We find that electrostatic detection is likely to be a significantly easier prospect for microtubules than it is for actin
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