Fusion of polymer-coated liposomes and centrifugally spun microfibers as hybrid materials to enhance sustained release.

Liposomes are employed for the delivery of molecular cargo in several classes of systems. For instance, the embedding of loaded liposomes in polymeric fibrous scaffolds has enabled the creation of hybrid materials that mimic biological membranes. Liposomes with unmodified surfaces have been predominantly integrated into fibers, which leads to instabilities due to interfacial incompatibility.

Insights into the mechanism of crotamine and potential targets involved in obesity-related metabolic pathways.

Crotamine (Ctm) is a peptide isolated from Crotalus durissus terrificus venom. This molecule has been demonstrated to diminish body weight gain and enhance browning in adipose tissue, glucose tolerance, and insulin sensitivity; hence, it has been postulated as an anti-obesogenic peptide. However, the mechanism to elicit the anti-obesogenic effects has yet to be elucidated.

Modulation of Phospholipase A Membrane Activity by Anti-inflammatory Drugs.

The phospholipase A (PLA) superfamily consists of lipolytic enzymes that hydrolyze specific cell membrane phospholipids and have long been considered a central hub of biosynthetic pathways, where their lipid metabolites exert a variety of physiological roles. A misregulated PLA activity is associated with mainly inflammatory-derived pathologies and thus has shown relevant therapeutic potential. Many natural and synthetic anti-inflammatory drugs (AIDs) have been proposed as direct modulators of PLA activity.

Linoleic acid improves PIEZO2 dysfunction in a mouse model of Angelman Syndrome.

Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability and atypical behaviors. AS results from loss of expression of the E3 ubiquitin-protein ligase UBE3A from the maternal allele in neurons. Individuals with AS display impaired coordination, poor balance, and gait ataxia.

Ca-mediated enhancement of anesthetic diffusion across phospholipid multilamellar systems.

Although sharing common properties with other divalent cations, calcium ions induce fine-tuned electrostatic effects essential in many biological processes. Not only related with protein structure or ion channels, calcium is also determinant for other biomolecules such as lipids or even drugs. Cellular membranes are the first interaction barriers for drugs.

The cut-off effect of n-alcohols in lipid rafts: A lipid-dependent phenomenon.

n-Aliphatic alcohols act as anesthetics only up to a certain chain length, beyond which its biological activity disappears. This is known as the 'cut-off' phenomenon. Although the most accepted explanation is based on action sites in membrane proteins, it is not well understood why alcohols alter their functions.

Dietary fatty acids fine-tune Piezo1 mechanical response.

Mechanosensitive ion channels rely on membrane composition to transduce physical stimuli into electrical signals. The Piezo1 channel mediates mechanoelectrical transduction and regulates crucial physiological processes, including vascular architecture and remodeling, cell migration, and erythrocyte volume. The identity of the membrane components that modulate Piezo1 function remain largely unknown.

Structure-function analyses of the ion channel TRPC3 reveal that its cytoplasmic domain allosterically modulates channel gating.

The transient receptor potential ion channels support Ca permeation in many organs, including the heart, brain, and kidney. Genetic mutations in transient receptor potential cation channel subfamily C member 3 (TRPC3) are associated with neurodegenerative diseases, memory loss, and hypertension. To better understand the conformational changes that regulate TRPC3 function, we solved the cryo-EM structures for the full-length human TRPC3 and its cytoplasmic domain (CPD) in the apo state at 5.

Purification and Reconstitution of TRPV1 for Spectroscopic Analysis.

Polymodal ion channels transduce multiple stimuli of different natures into allosteric changes; these dynamic conformations are challenging to determine and remain largely unknown. With recent advances in single-particle cryo-electron microscopy (cryo-EM) shedding light on the structural features of agonist binding sites and the activation mechanism of several ion channels, the stage is set for an in-depth dynamic analysis of their gating mechanisms using spectroscopic approaches. Spectroscopic techniques such as electron paramagnetic resonance (EPR) and double electron-electron resonance (DEER) have been mainly restricted to the study of prokaryotic ion channels that can be purified in large quantities.

Cryo-EM structure of the cytoplasmic domain of murine transient receptor potential cation channel subfamily C member 6 (TRPC6).

The kidney maintains the internal milieu by regulating the retention and excretion of proteins, ions, and small molecules. The glomerular podocyte forms the slit diaphragm of the ultrafiltration filter, whose damage leads to progressive kidney failure and focal segmental glomerulosclerosis (FSGS). The canonical transient receptor potential 6 (TRPC6) ion channel is expressed in the podocyte, and mutations in its cytoplasmic domain cause FSGS in humans.

Omega-3 Fatty Acids Modulate TRPV4 Function through Plasma Membrane Remodeling.

Dietary consumption of ω-3 polyunsaturated fatty acids (PUFAs), present in fish oils, is known to improve the vascular response, but their molecular targets remain largely unknown. Activation of the TRPV4 channel has been implicated in endothelium-dependent vasorelaxation. Here, we studied the contribution of ω-3 PUFAs to TRPV4 function by precisely manipulating the fatty acid content in Caenorhabditis elegans.

Expression and Purification of the Pain Receptor TRPV1 for Spectroscopic Analysis.

The transient receptor potential vanilloid 1 (TRPV1) channel is an essential component of the cellular mechanism through which noxious stimuli evoke pain. Functional and structural characterizations of TRPV1 shed light on vanilloid activation, yet the mechanisms for temperature and proton gating remain largely unknown. Spectroscopic approaches are needed to understand the mechanisms by which TRPV1 translates diverse stimuli into channel opening.

Pentobarbital modifies the lipid raft-protein interaction: A first clue about the anesthesia mechanism on NMDA and GABA receptors.

Recent studies have shown that anesthetic agents alter the physical properties of lipid rafts on model membranes. However, if this destabilization occurs in brain membranes, altering the lipid raft-protein interaction, remains unknown. We analyzed the effects produced by pentobarbital (PB) on brain plasma membranes and lipid rafts in vivo.

Sterilization by Cooling in Isochoric Conditions: The Case of Escherichia coli.

High hydrostatic pressure (HHP) affects the structure, metabolism and survival of micro-organisms including bacteria. For this reason HHP is a promising treatment in the food industry. The aim of this work is to evaluate the effect of high pressure, under isochoric cooling conditions, on Escherichia coli, where such high pressure develops due to the fact water cannot expand.

Anesthetic diffusion through lipid membranes depends on the protonation rate.

Hundreds of substances possess anesthetic action. However, despite decades of research and tests, a golden rule is required to reconcile the diverse hypothesis behind anesthesia. What makes an anesthetic to be local or general in the first place? The specific targets on proteins, the solubility in lipids, the diffusivity, potency, action time? Here we show that there could be a new player equally or even more important to disentangle the riddle: the protonation rate.

The interaction of local anesthetics with lipid membranes.

Molecular Dynamic Simulations are performed to evaluate the interaction of lidocaine, procaine and tetracaine with a lipid membrane. The main interest is to evaluate the structural changes produced by these local anesthetics in the bilayers. Penetration trajectories, interaction energies, entropy changes and an order parameter are calculated to quantify the destabilization of the lipid configurations.

The influence of non polar and polar molecules in mouse motile cells membranes and pure lipid bilayers.

We report an experimental study of mouse sperm motility that shows chief aspects characteristic of neurons: the anesthetic (produced by tetracaine) and excitatory (produced by either caffeine or calcium) effects and their antagonic action. While tetracaine inhibits sperm motility and caffeine has an excitatory action, the combination of these two substances balance the effects, producing a motility quite similar to that of control cells. We also study the effects of these agents (anesthetic and excitatory) on the melting points of pure lipid liposomes constituted by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and dipalmitoyl phosphatidic acid (DPPA).

Noble gases in pure lipid membranes.

The mechanism of how a noble gas modifies the excitability of nerve cells and how such excitability can be recovered under hyperbaric pressure remains unclear. Here we present a calorimetric study where the melting point depression of pure lipid membranes induced by noble gases and its recovery with a hydrostatic pressure is addressed. A correlation is found between the electric polarizability (α) of these gases and their effect on the melting transition of the membranes.

A thermal study of cellular motility by optical time-resolved correlation.

The study of motor properties of cells under appropriate physical-chemical conditions is a significant problem nowadays. The standard techniques presently used do not allow to evaluate neither large samples nor to control their thermodynamic conditions. In this work, we report a cell motility sensor based on an optical technique with a time-resolved correlation, adapted in a system able to study several samples simultaneously.

Acoustic gaps in a chain of magnetic spheres.

Acoustic gaps are normally observed in granular inhomogeneous structures made of composite materials. The modulation of the elastic properties in such media creates the coherent effects of scattering and interference that ultimately lead to frequency intervals where sound propagation is forbidden. Contrastingly, we report here an experimental observation of acoustic gaps in homogeneous media; specifically, in granular chains.