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

Abstract

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.

Correlation Force Spectroscopy for Single Molecule Measurements

“…In another study, Bippes et al [37] investigated the viscoelastic properties of dextran while stretching a single chain of the molecule and collecting the thermal fluctuations of the 6 cantilever. They report a good agreement between their results and results of Kawakami et al [36]. As part of device evaluation and preliminary results, I also studied dextran molecule and found qualitative agreement in mechanical properties of this molecule with previous studies.…”

“…Recognizing this problem, Kawakami et al [36] developed a modification of the basic AFM experiment in which they exploited the thermal vibration. They measured the thermally-stimulated power spectral density (PSD) of one AFM cantilever rather than the static deflection.…”

“…Ref. [36]), so there are known properties, and a known method for straddling the molecule between an AFM tip and a solid. The method is to coat the solid with a layer of dextran, then to touch this layer with an AFM tip.…”

“…Sample fits of equations (7.9) to (7.12) to experimental data are shown in Figure [36]) and dynamic CF-mode using the same data. Figure 7-7-b shows the measured polymer friction coefficient as a function of force.…”

Can Dissipative Properties of Single Molecules Be Extracted from a Force Spectroscopy Experiment?

“…A number of experiments to measure the dissipative properties of single molecules (i.e., their internal friction) have been reported (see, e.g., (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)). One of the most straightforward methods employs small-amplitude dithering of an atomic force microscope (AFM) tip and measurements of the phase changes of this oscillatory system in the course of molecule stretching.…”