Chemists used to sample Avogadro numbers of molecules for their experiments.
The properties they measured were averaged on the entire ensemble of those
molecules and over all conformations accessible to them. A new exciting
dimension has been opened: a single molecule can be simultaneously touched
and observed, and then also dissected and mechanically manipulated to drive
its structure towards new conformations and states that otherwise can be
very hard to reach. Conformational rearrangements from these states and
thermal fluctuations of supercoiled and linear DNA molecules were followed
and observed in fluid, in real time, with a Scanning Force Microscope (SFM).
Local curvatures and flexibilities of the chains were monitored and analyzed
at the single molecule level and their modulation by the sequence was studied.
The spatial resolution of SFM settles this analysis in the nanometer scale.
This is the length scale of the long-range recognition of conformational
properties and dynamics labeled "indirect-read out". This recognition mechanism
of not-so-local conformational properties is used by the DNA-tracking-proteins
during their search of specific binding sites along the DNA chain. This
work shows how topics of polymer chemistry and biology can be transferred
to the single-molecule level.
The capability of controlling the adsorption and reactivity of single dna molecules on surfaces opens the perspective of creating a novel class of nanotechnologies of the nucleic acids.
References
G. Zuccheri, R. Thei Dame, M. Aquila, I. Muzzalupo, B. Samori', Conformational fluctuations of supercoiled DNA molecules observed in real time with a scanning force microscope, Applied Physics A 1998, 66, S585-S589
B. Samori', Stretching, tearing and dissecting single molecules of DNA, Angew. Chem. Int. Ed. Engl., 1998, 37, 2198-2200