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Although native mass spectrometry is widely applied to monitor chemical or thermal protein denaturation, it is not clear to what extent it can inform about alkali-induced unfolding. Here, we probe the relationship between solution- and gas-phase structures of proteins under alkaline conditions. Native ion mobility-mass spectrometry reveals that globular proteins are destabilized rather than globally unfolded, which is supported by solution studies, providing detailed insights into alkali-induced unfolding events. Our results pave the way for new applications of MS to monitor structures and interactions of proteins at high pH.

The interplay between the amyloid-β (Aβ) peptide and cellular membranes have been proposed as an important mechanism for toxicity in Alzheimer's disease (AD). Membrane environments appear to influence Aβ aggregation and may stabilize intermediate Aβ oligomeric states that are considered to be neurotoxic. One important role for molecular biophysics within the field of Aβ studies is to characterize the structure and dynamics of the Aβ peptide in various states, as well as the kinetics of transfer between these states. Because biological cell membranes are very complex, simplified membrane models are needed to facilitate studies of Aβ and other amyloid proteins in lipid environments. In this review, we examine different membrane-mimetic systems available for molecular studies of Aβ. An introduction to each system is given, and examples of important findings are presented for each system. The benefits and drawbacks of each system are discussed from methodical and biological perspectives.