Neurodegenerative diseases like Alzheimer’s disease (AD) are characterized by the formation of proteinaceous fibrillar aggregates commonly classified as amyloids. The presence of neuritic amyloid plaques containing aggregated β-amyloid (Aβ) is also a distinctive feature of AD. Lipid membranes or bilayers are the structural basis of biological membranes. Acting as a model surface, lipid bilayers can provide insight into protein misfolding and aggregation on physiological surfaces. We hypothesize that varied lipid membrane composition will result in diverse aggregation kinetics and protein morphology of Aβ, further modulating lipid membrane nanomechanical properties (i.e. modulus, adhesion, etc.) and protein-lipid interactions. To test this hypothesis we used atomic force microscopy (AFM) to create various lipid bilayer in situ environments and subsequently imaged the interaction and morphological changes between the bilayer and aggregation of Aβ1-40. The imaging capability of AFM makes it possible to characterize the nanomechanical properties of lipid surfaces exposed to various proteins. Here AFM was used to measure peptide-lipid interactions of Aβ1-40 with lipid bilayers comprised of neutral total brain lipid extract (TBLE), and neutral dimyristoylphosphatideylcholine (DMPC). These lipids were chosen due to their differences in composition, but similarity in surface charge. With AFM, we observed distinct changes in Aβ1-40 aggregate morphology and kinetics due to diverse interactions with each lipid composition. We were able to quantify the peptide-lipid interaction with a measurement of percent area disruption, as well as percent colorimetric response through the use of a biosensing colorimetric assay comprised of lipids integrated within a polydiacetylene matrix. These studies demonstrated how amyloidogenic protein interaction with lipid membranes is significant because it is a driving force in protein aggregation. This interaction may provide detailed understanding into the influence of cellular surfaces on protein aggregation in neurodegenerative diseases.

Characterizing the nanomechanical properties of β-amyloid aggregation on various lipid surfaces by atomic force microscopy

253rd National Meeting (2017)

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