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Biological Force Standards

The Tom Perkins group investigates biological molecules as force standards at the pico-Newton scale (10-12 N). The forces applied by Atomic Force Microscopes (AFMs) and optical traps cannot be directly linked to an internationally accepted force standard (i.e., SI traceable) over the force range from pico-Newtons (10-12 N) to nano-Newtons (10-9 N). For AFM applications, SI traceability currently relies on a force transfer in a NIST-operated electrostatic force balance that provides a micro-Newton (10-6 N) force calibration with nano-Newton sensitivity. This calibration is three to six orders of magnitude higher than the force regime under investigation by the group. The group’s study of biological molecules as intrinsic force standards is part of the larger NIST project.

Biological molecules, in general, and DNA, in particular, exhibit some unique properties that make them excellent candidates to be force standards. First, DNA undergoes a mechanical phase transition around 65 pN, in which its extension almost doubles in a narrow force range (5 pN). Second, DNA hairpins (loops) can flicker between an open and closed state at a very specific force (e.g., 12.1 pN). A 0.1 pN change in this force can lead to >20% change in the hairpin’s probability of being open.

In addition to these interesting and attractive mechanical attributes, a DNA force standard could readily be distributed. First, the high fidelity of enzymatic replication guarantees a uniform molecule that does not vary in size or composition from batch to batch, even at the atomic level. Second, DNA is made with standard biochemical assays, so it is cheap and easy to produce. Third, attaching chemical "handles" is simple and allows quick coupling of the DNA to force probes. The Perkins group is currently exploring different DNA hairpins and the "over-stretch transition" as potential force standards. They are working on improving the precision and accuracy of their measurements.