Probing the nanomechanical properties of lipid membranes: The effect of trodusquemine.

We have used atomic force spectroscopy to study the effects of trodusquemine, a promising drug candidate against neurodegenerative disorders, on the mechanical properties of supported lipid bilayers (SLBs) mimicking neuronal membranes. These biomimetic SLBs exhibit a phase separation between a disordered, fluid phase and an ordered, condensed phase. Through an accurate analysis, taking into account the thickness of the bilayer and correcting for the influence of the rigid substrate, we were able to determine the intrinsic values of the bilayer Young's modulus in the different phases as a function of trodusquemine concentration. We found that both the bilayer's Young's modulus, which represents the stiffness of the lipid layer, and the force required to penetrate the membrane, or breakthrough force, increase in the presence of trodusquemine. This increase in mechanical strength could contribute to an increased resistance of the membranes to the toxic action of misfolded protein oligomers.