Amyloid- $\beta$ aggregates play a causative role in Alzheimer’s disease. These aggregates are a product of the physical environment provided by the basic neuronal membrane, composed of a lipid bilayer. The intrinsic properties of the lipid bilayer allow amyloid- $\beta$ peptides to nucleate and form well-ordered cross- $\beta$ sheets within the membrane. Here, we correlate the aggregation of the hydrophobic fragment of the amyloid- $\beta$ protein, $A{\beta }_{25-35}$ , with the hydrophobicity, fluidity, and charge density of a lipid bilayer. We summarize recent biophysical studies of model membranes and relate these to the process of aggregation in physiological systems.

The physical effects of small sugars on membranes have been studied for decades, primarily because of their membrane stabilization in cold or dehydrated environments. We studied the effects of up to 20 mol% glucose in bilayers made of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) at low hydration by combining X-ray diffraction and Molecular Dynamics (MD) simulations. In agreement with previous studies, we observe membrane thinning at low and membrane thickening at high sugar concentrations. Glucose was found to preferentially localize to the outer head region of phospholipid bilayers at all concentrations, and partitioning of sugar in the membranes was found to monotonically increase with increasing sugar concentration. While the number of gauche defects in the lipid acyl tails and the lipid packing in the presence of sugar resembled values of a fluid lipid bilayer, tail dynamics, as assessed by autocorrelation of the carbon atoms in the phospholipid tails, were slowed down significantly with increasing glucose content. Thus, our findings suggest that sugar leads to a a disordered, glassy state of the hydrophobic membrane core. The non-monotonic effect of glucose on membrane thickness was found to be an effect of fluidification at low concentrations and decreased interdigitation in the higher sugar concentration regime.

Amyloid-β peptides interact with cell membranes in the human brain and are associated with neurodegenerative diseases, such as Alzheimer’s disease. An emerging explanation of the molecular mechanism, which results in neurodegeneration, places the cause of neurotoxicity of the amyloid- peptides on their potentially negative interaction with neuronal membranes. It is known that amyloid-β peptides interact with the membrane, modifying the membrane’s structural and dynamic properties. We present a series of X-ray diffraction experiments on anionic model lipid membranes containing various amounts of cholesterol. These experiments provide experimental evidence for an interaction of both the full length amyloid-β_1-42 peptide, and the peptide fragment amyloid-β_22-40 with anionic bilayer containing cholesterol. The location of the amyloid-β peptides was determined from these experiments, with the full length peptide embedding into the membrane, and the peptide fragment occupying 2 positions—on the membrane surface and embedded into the membrane core.

There is an urgent quest for improved heart health. Here, we review how neutron radiation can provide insight into the molecular basis of heart health. Lower cholesterol, a daily intake of aspirin and supplemental vitamin E are argued to all improve heart health. However, the mechanisms behind these common regimens, and others, are not entirely understood. It is not clear why a daily intake of aspirin can help some people with heart disease, and the benefits of vitamin E in the treatment of reperfusion injury have been heavily debated. The molecular impact of cholesterol in the body is still a hot topic. Neutron scattering experiments present a unique opportunity for biophysicists attempting to address these problems. We review some recently published studies that are advancing our understanding of how cholesterol, vitamin E and aspirin work at the molecular level, by studying the impact of these molecules on the cell membrane. These insights engage the broader health science community with new ways of thinking about these molecules.

It was recently reported that static magnetic fields increase lipid order in the hydrophobic membrane core of dehydrated native plant plasma membranes [Poinapen, Soft Matter 9:6804-6813, 2013]. As plasma membranes are multicomponent, highly complex structures, in order to elucidate the origin of this effect, we prepared model membranes consisting of a lipid species with low and high melting temperature. By controlling the temperature, bilayers coexisting of small gel and fluid domains were prepared as a basic model for the plasma membrane core. We studied molecular order in mixed lipid membranes made of dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) using neutron diffraction in the presence of strong static magnetic fields up to 3.5 T. The contribution of the hydrophobic membrane core was highlighted through deuterium labeling the lipid acyl chains. There was no observable effect on lipid organization in fluid or gel domains at high hydration of the membranes. However, lipid order was found to be enhanced at a reduced relative humidity of 43%: a magnetic field of 3.5 T led to an increase of the gel signal in the diffraction patterns of 5%. While all biological materials have weak diamagnetic properties, the corresponding energy is too small to compete against thermal disorder or viscous effects in the case of lipid molecules. We tentatively propose that the interaction between the fatty acid chains’ electric moment and the external magnetic field is driving the lipid tails in the hydrophobic membrane core into a better ordered state.