In order to reveal the backbone amide bands of Aβ underneath the large water background, we determined the 2 nd derivatives of the spectra (Figure , shown below the corresponding SEIRA spectra). As the 2 nd derivative is a measure for the curvature of a signal, determining 2 nd derivative spectra considerably enhances narrow signals over broad ones and is therefore commonly used in IR spectroscopy. In our case, we can now readily detect multiple amide I signals in the 1700 -1600 cm -1 region, which are due to the C=O stretch of the Aβ peptide backbone, along with amide II bands in the 1600 -1500 cm -1 range due a combination of backbone CN stretches and NH bends. In particular the amide I is very sensitive to the secondary structure, enabling us to observe distinct structural differences of Aβ between the different membrane systems. Interestingly, inspecting the 2 nd derivatives in the tMLM system in Figure , where Aβ cannot insert into the membrane, we detect two dominating peaks at about 1694 and 1635 cm -1 , which are marker bands for antiparallel β-sheet structures, due to symmetric and antisymmetric couplings of the amide C=O stretches, respectively. Instead, for the tBLM that allows incorporation, we detect only the 1635 cm -1 band in the absence of the 1694 cm -1 signal, a specific marker for parallel β-sheets. This difference between tMLM and tBLM systems suggests that the ability for Aβ to penetrate the membrane has considerable consequences on the antiparallel to parallel βsheet transition, an important step along the misfolding trajectory. In addition to the β-sheet signals, the 2 nd derivatives also show minor features in the range of 1680 -1650 cm -1 , which can be assigned to combinations of unstructured peptides (random coils) as well as α-helices and β-turns. Along with these signals we also note an amide II peak at 1560 cm -1 and 1530 cm -1 , which is less sensitive to the secondary structure. As shown in Figure and S4, we observe a similar difference of amide I shapes between tMLMs and tBLMs for neutral lipids albeit with lesser absolute amount of Aβ in β-sheet folds. This suggests that the modulation of the antiparallel to parallel β-sheet transition is affected to much lesser degree by lipid charge than by the ability to insert into the membrane. At positively charged lipid membranes, we do not detect any amide I signals specific to β-sheets (Figure ).