Structural and Mechanical Response of Two-Component Photoswitchable Lipid Bilayer Vesicles.

Optical control of phospholipids is an attractive option for the rapid, reversible, and tunable manipulation of membrane structure and dynamics. Azo-PC, a lipid with an azobenzene group within one acyl chain, undergoes a light-induced trans-to-cis isomerization and thus arises as a powerful tool for manipulating lipid order and dynamics. Here, we report on vesicle-scale micropipette measurements and atomistic simulations to probe the elastic stretching modulus, water permeability, toughness, thickness, and membrane area upon isomerization. We investigated both dynamics and steady-state properties. In pure azo-PC membranes, we found that the molecular area in trans was 16% smaller than that in cis, the membrane's stretching modulus kA was 2.5 ± 0.3 times greater, and the water permeability PW was 3.5 ± 0.5 times smaller. We also studied mixtures of azo-PC with the miscible, unsaturated lipid DOPC. Atomistic molecular dynamics simulations show how the membrane thickness, chain order, and correlations across membrane leaflets explain the experimental data. Together, these data show how one rotating bond changes the molecular- and membrane-scale properties. These results will be useful for photopharmacology and for developing new materials whose permeability, elasticity, and toughness may be switched on demand.

Single Ion-Channel Analysis in Droplet Interface Bilayer.

Droplet interface bilayer (DIB) is a method of fabricating lipid bilayer membrane by contacting two aqueous droplets coated with a monolayer of lipid molecules in oil media. Lipids coat the droplet surface either by vesicles fusing to the water-oil interface from the droplet side or diffusing toward the interface from the oil side, thereby forming a lipid monolayer. With the DIB technique, nanoliter amounts of aqueous solution is needed and one may obtain two different compositions of monolayers to form asymmetric bilayer which is difficult to replicate by other in vitro lipid membrane methods. Here, a DIB-based protocol is reported to fabricate a stable lipid bilayer membrane to perform single-channel electrophysiology on a pore-forming toxin.

Is amyloid-ß an innocent bystander and marker in Alzheimer's disease? Is the liability of multivalent cation homeostasis and its influence on amyloid-ß function the real mechanism?

Two decades of the amyloid-ß (Aß) hypothesis in Alzheimer's disease (AD) and the prominence of Aß-targeting strategies have yet to meet the levels of original expectation. Disappointing results in numerous Phase II/III studies have called for a re-examination of the validity of the Aß-targeting approaches as an intervention strategy in AD. The mid-life onset of chronic conditions (e.g., hypertension, diabetes, insulin intolerance, and depression nominated as risk factors for the later development of AD) points to the possibility that each condition could involve mechanisms, which while relatively modest over a short-term, could have significant accumulative effects. What may also not be fully appreciated is that a number of these conditions involve potential disturbances to multivalent cations (MC) levels through various mechanisms such as autophagy, oxidative stress, and apoptosis. Furthermore, some MCs have intimate associations with the mechanisms by which Aß pathology manifests. Considering various lines of evidence and incorporating statistical analysis on Disability-Adjusted Life Years (DALYs) data of both causes of and prevalence of multifactorial risk factors in different world regions, we propose an MC hypothesis for AD. More specifically, we suggest that MC imbalance marks many chronic conditions and because of their involvement with Aß pathology, could reflect that Aß may be a vital manifestation and marker of underlying MC imbalance. Thus, careful targeting of MC imbalance may provide an alternative or complementary interventional approach to current Aß treatment strategies.

Alzheimer's disease: pathophysiology and applications of magnetic nanoparticles as MRI theranostic agents.

Alzheimer's disease (AD) is the most common form of dementia. During the recent decade, nanotechnology has been widely considered, as a promising tool, for theranosis (diagnosis and therapy) of AD. Here we first discuss pathophysiology and characteristics of AD with a focus on the amyloid cascade hypothesis. Then magnetic nanoparticles (MNPs) and recent works on their applications in AD, focusing on the superparamagnetic iron oxide nanoparticles (SPIONs), are reviewed. Furthermore, the amyloid-nanoparticle interaction is highlighted, with the scope to be highly considered by the scientists aiming for diagnostics and/or treatment of AD employing nanoparticles. Furthermore, recent findings on the "ignored" parameters (e.g., effect of protein "corona" at the surface of nanoparticles on amyloid-ß (Aß) fibrillation process) are discussed.