Evaluation of intrinsic Young's modulus and stiffening effect of trodusquemine in phase-separated supported lipid bilayers.

The measurement of the Young's modulus of thin, soft films on solid support is affected by the presence of the so-called bottom effect artefact, which arises from the presence of a rigid substrate and increases the observed value of the elastic modulus of the sample. Here we measured the Young's modulus of a multicomponent, phase-separated supported lipid bilayer mimicking the biological membrane in the absence and presence of various concentrations of trodusquemine, which is a molecule with potential applications against neurodegenerative diseases. Applying the Garcia and Garcia theory for bottom effect correction on a multiphase system enabled the evaluation of the intrinsic Young's modulus of the lipid bilayer, decoupling it from the substrate contribution. We found that at all trodusquemine concentrations tested both the ordered and disordered phases of the lipid bilayer increase their rigidity. The highest increase was measured at the lowest concentration tested of 1 μM, supporting the relevance and therapeutic potential of this class of molecules at physiologically achievable doses. Overall, this study provides a methodological framework for investigating the mechanical properties of supported thin films endowed of a complex texture.