By mole, cholesterol is the most abundant component of animal cell plasma membranes. Many membrane proteins have been shown to be functionally dependent on cholesterol, several of which have also been shown to bind cholesterol at well-defined locations on their membrane-facing surface. In this work, a combination of coarse-grained "Martini" and all-atom simulations are used to identify two, to our knowledge, new cholesterol-binding sites on the A adenosine receptor, a G-protein-coupled receptor that is a target for the treatment of Parkinson's disease. One of the sites is also observed to bind cholesterol in several recent, high-resolution crystal structures of the protein, and in the simulations, interacts with cholesterol only when bound to the inverse agonist ZM241385. Cataloguing cholesterol-binding sites is a vital step in the effort to understand cholesterol-dependent function of membrane proteins. Given that cholesterol content in plasma membranes varies with cell type and on administration of widely prescribed pharmaceuticals, such as statins, understanding cholesterol-dependent function is an important step toward exploiting membrane compositional variation for therapeutic purposes.

No abstract

In this paper, we propose a novel Weakly-Supervised Dual Clustering (WSDC)

Sequence-determined bottlebrush polymers are precisely, efficiently and conveniently synthesized.

Reported is an intriguing advance in living anionic polymerization (LAP) by a"locked-unlocked" mechanism in which the living anionic species can be quantitatively locked by end-capping with 1-(tri-isopropoxymethylsilylphenyl)-1-phenylethylene (DPE-Si(O-iPr) 3 )and can be unlocked by adding the key,s odium 2,3-dimethylpentan-3-olate (NaODP). These new insights into this mechanismw ere carefully confirmed by designing reactions involving sequential feeding of quantitative DPE-Si(O-iPr) 3 and traditional monomers mixed with NaODP,a nd subsequently characterizing the corresponding samples,taken during the feeding process,byGPC,NMR, and MALDI-TOF-MS techniques.T he switch from the locked to unlocked state was clearly confirmed by these characterization techniques.T he putative locked-unlockedm echanism in the LAP was simulated by the Gaussian method. This intriguing mechanistic finding of LAP reactions is expected to supplement the existing knowledge and facilitate the tailoring of specific structures for these polymerizations.

When a range of lipid bilayers are melted to the disordered fluid phase from the (much less permeable) ordered gel phase, their permeability to a variety of permeants shows a peak at the transition temperature and drops off with increasing temperature, rather than just rising as melting proceeds. To explore this anomalous behavior, a simulated coarse-grained lipid membrane model that exhibits a phase transition upon expansion or compression was studied to determine how the permeation rate of a simple particle depends on the phase composition in the two-phase region and on particle size. The permeation rate and each phase's area fraction and area density could be directly calculated, along with the probability that the permeant would cross in either phase or in interfacial regions. For large permeants and system sizes, conditions could be found where permeability increases upon compression of the bilayer. Permeation was negligible in the gel phase and, in contrast to the predictions of the "leaky interface" hypothesis, was not enriched in interfacial regions. The anomalous effect could instead be attributed to an increase in the area per lipid of fluid-phase domains. This result motivated a model for the decrease in effective permeability barrier through fluid-phase domains arising from a decrease in the length of the gel/fluid interface at the midpoint of a permeation event.

Due to concerns regarding fuel consumption and environmental issues arising from the use of elastomers, particularly in the automobile industry, we investigated the strategy of fabricating elastomers based on the biogenic β-myrcene and styrene using living anionic polymerization and successfully cross-linked these elastomers with sulfur. Furthermore, the dynamic viscoelastic and mechanical behaviors of these cured elastomers were investigated. Amazingly, the damping factor (tan δ) of the homopolymer of β-myrcene increased to 2.8 and exhibited a good damping potential. In addition, the satisfying wet skid resistance and rolling resistance performance were obtained for the copolymer with styrene. Meanwhile, the tensile strength and elongation at break of the copolymer were approximately 1.4 MPa and 230%, respectively. Moreover, the mechanical performance of the copolymer was distinctly improved after reinforcement with carbon black or silica. In particular, the tensile strength of copolymers filled with 30 phr carbon black or silica increased by 220–378%. On the basis of preliminary results, we believe that the elastomer with biogenic myrcene is a versatile and outstanding candidate future elastomer material.

A reversible on/off switch to control chain growth in a living anionic polymerization is a meaningful challenge for its profound potential in both polymerization mechanisms and the preparation of advanced materials. Herein, we report a thermally controlled on/off switch for chain propagation in an anionic polymerization that is realized with a 1-cyclopropylvinylbenzene (CPVB) monomer. Interestingly, the specific ring-opening manner and thermal sensitivity are shown in the addition reaction of CPVB with the initiator or living chains. The ring opening of the cyclopropyl group in CPVB is observed to be a possible anion migrated ring-opening mechanism in the addition reactions. Additionally, the polymerization of CPVB occurs only at high temperature, and the chain growth constant kCC is near 0 at 20 °C, 0.0039 (L/mol)1/2 min–1 at 50 °C, and 0.016 (L/mol)1/2 min–1 at 60 °C. Thus, based on its unique characteristics, an ingenious design of “heat (60 °C)–cool (20 °C)” cycles is employed to achieve a thermally controlled on/off switch for chain growth in an anionic polymerization. It is expected that this finding can provide new insights into both controlling the monomer or multiblock sequence and raise a novel technique to stage control the chain growth with temperatures in living anionic polymerization.