Prospects for single-molecule electrostatic detection in molecular motor gliding motility assays

TL;DR

This paper evaluates the feasibility of using single-molecule electrostatic detection with carbon nanotube transistors to monitor molecular motor filaments in gliding assays, potentially enabling more integrated and scalable nanotechnology applications.

Contribution

It provides a detailed analysis of the electrostatic detection potential for actin and microtubules, considering various experimental conditions and device configurations, highlighting microtubules as more promising targets.

Findings

Detection feasible with existing transistor technology under certain conditions.

Microtubules more detectable due to higher charge density and surface proximity.

Device design improvements can enhance detection sensitivity.

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 and 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.