Viscoelastic Properties of Single Polysaccharide Molecules Determined by Analysis of Thermally Driven Oscillations of an Atomic Force Microscope Cantilever

We report on single molecule measurements of the viscoelastic properties of the polysaccharide dextran using a new approach which involves acquiring the power spectral density of the thermal noise of an atomic force microscope cantilever while holding the single molecule of interest under force-clamp conditions. The attractiveness of this approach when compared with techniques which use forced oscillations under constant loading rate conditions is that it is a near-equilibrium measure of mechanical response which provides a more relevant probe of thermally driven biomolecular dynamics. Using a simple harmonic oscillator model of the cantilever-molecule system and by subtracting the response of the free cantilever taking into account hydrodynamic effects, the effective damping zetamol and elastic constant kmol of a single molecule are obtained. The molecular elasticity measured by this new technique shows a dependence on applied force that reflects the chair-boat conformational transition of the pyranose rings of the dextran molecule which is in good agreement with values obtained directly from the gradient of a conventional constant loading rate force-extension curve. The molecular damping is also seen to follow a nontrivial dependence on loading which we suggest indicates that it is internal friction and not work done on the solvent that is the dominant dissipative process.