Alzheimer's Disease (AD) is a neurodegenerative disorder that is prevalent among the elderly population. Aß protein has been heavily implicated in the pathogenesis of AD. This protein in its fibrillar form is a major component in the senile plaques that form on neuronal cellular membranes during the course of AD. Despite substantial efforts the exact mechanism of Aß toxicity towards a cell membrane is not well-understood. The determination of this mechanism, however, is of utmost importance, since the membrane presents the first site of Aß interaction with neurons, which in turn maybe the origin of Aß neurotoxicity. The purpose of this study was to find a lipid composition that can be used as a model of neuronal membrane for subsequent studies of the role of topographical heterogeneity (domain formation) on Aß-membrane interaction as related to AD. The lipids used in the study were 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), cholesterol (Chol), sphingomyelin (SM) and ganglioside GM1 (GM1). These lipids were combined in different proportions and deposited on a mica substrate to form supported monolayers. They were then imaged with an atomic force microscope (AFM) to determine if any of them exhibited domain formation. Three of the studied samples: POPC/POPG/SM 40:40:20 +5%Chol, POPC/SM/Chol 75:20:5 and POPC/SM/GM1/Chol 74:2:1:23 were found to possess interesting topography, rich in structural features: pores and domains. The average height difference between the domain features for each sample was found to be 0.58±015 nm, 0.61±0.12 nm and 0.27±0:07 nm.

Alzheimer's Disease (AD) is a neurodegenerative disorder that is prevalent among the elderly population. Aß protein has been heavily implicated in the pathogenesis of AD. This protein in its fibrillar form is a major component in the senile plaques that form on neuronal cellular membranes during the course of AD. Despite substantial efforts the exact mechanism of Aß toxicity towards a cell membrane is not well-understood. The determination of this mechanism, however, is of utmost importance, since the membrane presents the first site of Aß interaction with neurons, which in turn maybe the origin of Aß neurotoxicity. The purpose of this study was to find a lipid composition that can be used as a model of neuronal membrane for subsequent studies of the role of topographical heterogeneity (domain formation) on Aß-membrane interaction as related to AD. The lipids used in the study were 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), cholesterol (Chol), sphingomyelin (SM) and ganglioside GM1 (GM1). These lipids were combined in different proportions and deposited on a mica substrate to form supported monolayers. They were then imaged with an atomic force microscope (AFM) to determine if any of them exhibited domain formation. Three of the studied samples: POPC/POPG/SM 40:40:20 +5%Chol, POPC/SM/Chol 75:20:5 and POPC/SM/GM1/Chol 74:2:1:23 were found to possess interesting topography, rich in structural features: pores and domains. The average height difference between the domain features for each sample was found to be 0.58±015 nm, 0.61±0.12 nm and 0.27±0:07 nm.

Yes / Inhaled nanoparticles (NPs) are experienced by the first biological barrier inside the alveolus known as lung surfactant (LS), a surface tension reducing agent, consisting of phospholipids and proteins in the form of the monolayer at the air-water interface. The monolayer surface tension is continuously regulated by the alveolus compression and expansion and protects the alveoli from collapsing. Inhaled NPs can reach deep into the lungs and interfere with the biophysical properties of the lung components. The interaction mechanisms of bare gold nanoparticles (AuNPs) with the LS monolayer and the consequences of the interactions on lung function are not well understood. Coarse-grained molecular dynamics simulations were carried out to elucidate the interactions of AuNPs with simplified LS monolayers at the nanoscale. It was observed that the interactions of AuNPs and LS components deform the monolayer structure, change the biophysical properties of LS and create pores in the monolayer, which all interfere with the normal lungs function. The results also indicate that AuNP concentrations >0.1 mol% (of AuNPs/lipids) hinder the lowering of the LS surface tension, a prerequisite of the normal breathing process. Overall, these findings could help to identify the possible consequences of airborne NPs inhalation and their contribution to the potential development of various lung diseases. / University of Technology Sydney (UTS) FEIT Research Scholarship, UTS IRS (S.I.H.), 2018 Blue Sky scheme–Suvash Saha (Activity 2232368), N.S.G is supported by the Vice-Chancellor fellowship funded by QUT.

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