SmAP: Manipulating DNA by Ultrasound - Single-Molecules Go Acoustic

Abstract

The ability to study individual biomolecules in vitro has greatly expanded our knowledge of biological systems. Existing single-molecule techniques, such as optical and magnetic tweezers or atomic force microscopy, allow manipulation of individual biomolecules like DNA. They suffer from either being technically challenging or they offer low experimental throughput. We invented a novel lab-on-a-chip method to exert controllable forces on multiple DNA molecules simultaneously using ultrasound: single molecule Acoustical Pushing (smAP).smAP consists of a resonator integrated into a micro-fabricated fluidic chip. An acoustical pressure gradient is created homogeneously throughout the sample enabling to exert forces on DNA-tethered beads. By changing the amplitude of the driving voltage the pressure gradient can be altered, allowing sensitive control of the force applied to the DNA molecules.This approach makes it possible to apply forces up to hundreds of picoNewtons homogeneously over an area of several millimeter squared, allowing multiplexing to an unprecedented level. We validate this novel single-molecule method by recording force-distance curves of DNA molecules, both double- and single-stranded, in the presence of DNA-binding proteins. The simplicity and low cost makes smAP a widely accessible tool for biophysicists.