Physical Limits on the Mechanical Measurement of the Secondary Structure of Bio-molecules

The forces and lengths needed to mechanically denature a protein or nucleic acid are within the capabilities of the Atomic-Force Microscope. However, thermal fluctuations in the filament between the partially unfolded molecule and the force cantilever attenuate any measure of secondary structure on a length ~ (2/π2)(e/kBT)3/2(aA)1/2, where e is the energy required to liberate a length a of filament whose persistence length is A. Hence individual base pairs cannot readily be resolved but the stem-loop structure of RNA should be.