Biological Force Standards

The Tom Perkins group is working on the development of DNA and DNA hairpins as a force standard for the nano world. Polymers of DNA act like well-calibrated springs. DNA hairpins flicker between open and closed states at a characteristic force. In addition, DNA undergoes a sharp phase transition at ~65 pN. DNA’s unique mechanical properties plus the simplicity and fidelity with which it can be produced and distributed, make it an excellent candidate for a force standard.

To explore this idea further, the group recently tackled the challenge of precisely measuring the elasticity of short strands (~630 nm) of DNA. Initial experimental measurements revealed that short strands of DNA had systematic error of up to 18% — which is poor for a precision measurement. By teaming up with theorists from the Universities of Colorado and Pennsylvania, the group showed that the elasticity measurements were not the origin of the problem; rather the classic description of DNA elasticity was responsible. The Perkins team incorporated corrections into the original model to account for boundary conditions that become important at these small length scales. With this improved model, the researchers were able to reduce the systematic error of their elasticity measurements by threefold.

Next they undertook the challenge of measuring a tiny force with high precision. The group adopted laser stabilization techniques developed in JILA and applied them to optical-trapping microscopy. Using DNA hairpins, the researchers showed that with their improved instrumentation they could measure a 20% change in the probability of a DNA hairpin being open due to a 0.1 pN (<1%) force change, proving that biomolecules are indeed very sensitive to force.

However, much work remains to be done. Researchers must figure out how to further reduce systematic error rates of DNA elasticity measurements. More generally, they must find a way to improve the accuracy of the elasticity measurements to complement optical trapping’s excellent precision. In addition, the development of more precise and accurate measurements of single molecules is needed to enable detection of biological motion with atomic-scale sensitivity (0.1 nm).