Anesthetics significantly increase the amount of intramembrane water in lipid membranes.

The potency of anesthesia was directly linked to the partitioning of the drug molecules in cell membranes by Meyer and Overton. Many molecules interact with lipid bilayers and lead to structural and functional changes. It remains an open question which change in membrane properties is responsible for a potential anesthetic effect or if anesthetics act by binding to direct targets.

Photopolymerized Starchstarch Nanoparticle (SNP) network hydrogels.

Starch is an attractive biomaterial given its low cost and high protein repellency, but its use in forming functional hydrogels is limited by its high viscosity and crystallinity. Herein, we demonstrate the use of fully amorphous starch nanoparticles (SNPs) as functional hydrogel building blocks that overcome these challenges. Methacrylation of SNPs enables hydrogel formation via photopolymerization, with the low viscosity of SNPs enabling facile preparation of pre-gel suspensions of up to 35 wt% SNPs relative to <10 wt% with linear starch.

Lipid Rafts: Buffers of Cell Membrane Physical Properties.

Lateral organization of lipids in the cell membrane appears to be an ancient feature of the cell, given the existence of lipid rafts in both eukaryotic and prokaryotic cells. Currently seen as platforms for protein partitioning, we posit that lipid rafts are capable of playing another role: stabilizing membrane physical properties over varying temperatures and other environmental conditions. Membrane composition defines the mechanical and viscous properties of the bilayer.

Membrane-Modulating Drugs can Affect the Size of Amyloid-β Aggregates in Anionic Membranes.

The formation of amyloid-β plaques is one of the hallmarks of Alzheimer's disease. The presence of an amphiphatic cell membrane can accelerate the formation of amyloid-β aggregates, making it a potential druggable target to delay the progression of Alzheimer's disease. We have prepared unsaturated anionic membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS) and added the trans-membrane segment Aβ.

Aspirin locally disrupts the liquid-ordered phase.

Local structure and dynamics of lipid membranes play an important role in membrane function. The diffusion of small molecules, the curvature of lipids around a protein and the existence of cholesterol-rich lipid domains (rafts) are examples for the membrane to serve as a functional interface. The collective fluctuations of lipid tails, in particular, are relevant for diffusion of membrane constituents and small molecules in and across membranes, and for structure and formation of membrane domains.

Dynamically Cross-Linked Self-Assembled Thermoresponsive Microgels with Homogeneous Internal Structures.

The internal morphology of temperature-responsive degradable poly(N-isopropylacrylamide) (PNIPAM) microgels formed via an aqueous self-assembly process based on hydrazide and aldehyde-functionalized PNIPAM oligomers is investigated. A combination of surface force measurements, small angle neutron scattering (SANS), and ultrasmall angle neutron scattering (USANS) was used to demonstrate that the self-assembled microgels have a homogeneously cross-linked internal structure. This result is surprising given the sequential addition process used to fabricate the microgels, which was expected to result in a densely cross-linked shell-diffuse core structure.

Nanostructure of Fully Injectable Hydrazone-Thiosuccinimide Interpenetrating Polymer Network Hydrogels Assessed by Small-Angle Neutron Scattering and dSTORM Single-Molecule Fluorescence Microscopy.

Herein, we comprehensively investigate the internal morphology of fully injectable interpenetrating networks (IPNs) prepared via coextrusion of functionalized precursor polymer solutions based on thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) and nonthermoresponsive poly(vinyl pyrrolidone) (PVP) by reactive mixing using kinetically orthogonal hydrazone and thiosuccinimide cross-linking mechanisms. Small-angle neutron scattering, probing both the full IPN as well as the individual constituent networks of the IPN using index-matching, suggests a partially mixed internal structure characterized by PNIPAM-rich domains entrapped in a clustered PVP-rich phase. This interpretation is supported by super-resolution fluorescence microscopy (direct stochastic optical reconstruction microscopy) measurements on the same gels on a different length scale, which show both the overall phase segregation typical of an IPN as well as moderate mixing of PNIPAM into the PVP-rich phase.

Membrane Cholesterol Reduces Polymyxin B Nephrotoxicity in Renal Membrane Analogs.

Polymyxin B (PmB) is a "last-line" antibiotic scarcely used due to its nephrotoxicity. However, the molecular basis for antibiotic nephrotoxicity is not clearly understood. We prepared kidney membrane analogs of detergent-susceptible membranes, depleted of cholesterol, and cholesterol enriched, resistant membranes.

Membrane-Accelerated Amyloid-β Aggregation and Formation of Cross-β Sheets.

Amyloid- β 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- β peptides to nucleate and form well-ordered cross- β sheets within the membrane.

Curcumin Protects Membranes through a Carpet or Insertion Model Depending on Hydration.

Curcumin is the main ingredient in turmeric, a common Indian spice. Curcumin shows a broad spectrum of effects, including anti-Alzheimer's and antioxidant properties. An interaction between curcumin and lipid membranes has been speculated as the root cause of this activity, and the molecule is often proposed to protect the bilayer.

Giant axonal neuropathy alters the structure of keratin intermediate filaments in human hair.

Giant axonal neuropathy (GAN) follows an autosomal recessive genetic inheritance and impedes the peripheral and central nervous system due to axonal swellings that are packed with neurofilaments. The patients display a number of phenotypes, including hypotonia, muscle weakness, decreased reflexes, ataxia, seizures, intellectual disability, pale skin and often curled hair. We used X-ray diffraction and tensile testing to determine potential changes to the structure of keratin intermediate filaments (IFs) in the hair of patients with GAN.

Partitioning of caffeine in lipid bilayers reduces membrane fluidity and increases membrane thickness.

Caffeine is a small amphiphilic molecule, which is widely consumed as a stimulant to prevent fatigue, but is also used as a common drug adjuvant in modern medicine. Here, we show that caffeine interacts with unsaturated lipid membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). By combining X-ray diffraction and molecular dynamics simulations, we present evidence that caffeine partitions in lipid membranes and locates at the head group-tail group interface of the bilayers.

The Molecular Structure of Human Red Blood Cell Membranes from Highly Oriented, Solid Supported Multi-Lamellar Membranes.

We prepared highly oriented, multi-lamellar stacks of human red blood cell (RBC) membranes applied on silicon wafers. RBC ghosts were prepared by hemolysis and applied onto functionalized silicon chips and annealed into multi-lamellar RBC membranes. High resolution X-ray diffraction was used to determine the molecular structure of the stacked membranes.

Tuning the properties of injectable poly(oligoethylene glycol methacrylate) hydrogels by controlling precursor polymer molecular weight.

Tuning the properties of in situ-gelling injectable hydrogels based on synthetic polymers typically involves changing the chemistry of polymer backbones or the density of reactive functional groups on precursor polymers. Herein, we describe injectable, hydrazone crosslinked hydrogels based on well-defined poly(oligoethylene glycol methacrylate) (POEGMA) precursors prepared via reversible addition-fragmentation chain transfer (RAFT). These hydrogels have different molecular weights but similar functional group content, enabling engineering of hydrogel properties without substantially changing the chemistry of the precursor polymer.

A Cytosolic Amphiphilic α-Helix Controls the Activity of the Bile Acid-sensitive Ion Channel (BASIC).

The bile acid-sensitive ion channel (BASIC) is a member of the degenerin/epithelial Na channel (Deg/ENaC) family of ion channels. It is mainly found in bile duct epithelial cells, the intestinal tract, and the cerebellum and is activated by alterations of its membrane environment. Bile acids, one class of putative physiological activators, exert their effect by changing membrane properties, leading to an opening of the channel.

Swelling of phospholipid membranes by divalent metal ions depends on the location of the ions in the bilayers.

The Hofmeister series illustrates how salts produce a wide range of effects in biological systems, which are not exclusively explained by ion charge. In lipid membranes, charged ions have been shown to bind to lipids and either hydrate or dehydrate lipid head groups, and also to swell the water layer in multi-lamellar systems. Typically, Hofmeister phenomena are explained by the interaction of the ions with water, as well as with biological interfaces, such as proteins or membranes.

Structural Abnormalities in the Hair of a Patient with a Novel Ribosomopathy.

We report the biophysical characterization of hair from a patient with a de novo ribosomopathy. The patient was diagnosed with a mutation on gene RPS23, which codes for a protein which comprises part of the 40S subunit of the ribosome. The patient presents with a number of phenotypes, including hypotonia, autism, extra teeth, elastic skin, and thin/brittle hair.

The Lipid Bilayer Provides a Site for Cortisone Crystallization at High Cortisone Concentrations.

Cortisone is an injected anti-inflammatory drug that can cause painful side effects known as "steroid flares" which are caused by cortisone crystallizing at the injection site. We used molecular dynamics simulations and X-ray diffraction to study the interaction of cortisone with model lipid membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) at drug concentrations from 0 mol% to 50 mol%. Cortisone was found to partition in the lipid bilayer and locate in the hydrophilic to hydrophobic interface of the membranes.

Amyloid-β(25-35) peptides aggregate into cross-β sheets in unsaturated anionic lipid membranes at high peptide concentrations.

One of the hallmarks of Alzheimer's disease is the formation of protein plaques in the brain, which mainly consist of amyloid-β peptides of different lengths. While the role of these plaques in the pathology of the disease is not clear, the mechanism behind peptide aggregation is a topic of intense research and discussion. Because of their simplicity, synthetic membranes are promising model systems to identify the elementary processes involved.

The Position of Aβ22-40 and Aβ1-42 in Anionic Lipid Membranes Containing Cholesterol.

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.

Effect of shampoo, conditioner and permanent waving on the molecular structure of human hair.

The hair is a filamentous biomaterial consisting of the cuticle, the cortex and the medulla, all held together by the cell membrane complex. The cortex mostly consists of helical keratin proteins that spiral together to form coiled-coil dimers, intermediate filaments, micro-fibrils and macro-fibrils. We used X-ray diffraction to study hair structure on the molecular level, at length scales between ∼3-90 Å, in hopes of developing a diagnostic method for diseases affecting hair structure allowing for fast and noninvasive screening.

Strong Static Magnetic Fields Increase the Gel Signal in Partially Hydrated DPPC/DMPC Membranes.

NIt 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.

Neutron Scattering at the Intersection of Heart Health Science and Biophysics.

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.

Treatment age, dose and sex determine neuroanatomical outcome in irradiated juvenile mice.

Pediatric cranial radiation therapy can induce long-term neurocognitive deficits, the risk and severity of these deficits are amplified in females and in those individuals exposed at a younger age and/or those irradiated at higher doses. To investigate the developmental consequences of these factors in greater detail, male and female C57Bl/6J mice between infancy and late childhood (16 and 36 days) were irradiated at a single time point with a whole-brain dose of 0, 3, 5 or 7 Gy. In vivo and ex vivo magnetic resonance imaging (MRI) and deformation-based morphometry was used to identify radiation-induced volume differences.