Investigation of Protein/Lipid Interactions via Scanning Probe Acceleration Microscopy: Theory and Experiment

There is great interest in the application of proximal probe techniques to simultaneously image and measure mechancial properties of surfaces with nanoscale spatial resolution. There have been several innovations in generating time-resolved force interaction between the tip and surface while acquiring a tapping mode AFM image. These tip/sample forces contain information regarding mechanical properties of surfaces in an analogous fashion to a force curve experiment. Here, we demonstrate, via simulation, that the maximum and minimum tapping forces change with respect to the Young’s modulus and adhesiveness of a surface, but the roughness of the surfaces has no effect on the tapping forces. Using these changes in tapping forces, we determine the mechanical changes of a lipid membrane after exposure to a huntingtin exon1 (htt exon1) protein with an expanded polyglutamine (polyQ) domain. Expanded polyQ domains in htt is associated with Huntington’s disease, a genetic neurodegenerative disorder. The htt exon1 protein caused regions of increased surface roughness to appear in the lipid membrane, and these areas were associated with decreased elasticity and adhesion to the AFM probe.