Lateral diffusion, function, and expression of the slow channel congenital myasthenia syndrome αC418W nicotinic receptor mutation with changes in lipid raft components.

Lipid rafts, specialized membrane microdomains in the plasma membrane rich in cholesterol and sphingolipids, are hot spots for a number of important cellular processes. The novel nicotinic acetylcholine receptor (nAChR) mutation αC418W, the first lipid-exposed mutation identified in a patient that causes slow channel congenital myasthenia syndrome was shown to be cholesterol-sensitive and to accumulate in microdomains rich in the membrane raft marker protein caveolin-1. The objective of this study is to gain insight into the mechanism by which lateral segregation into specialized raft membrane microdomains regulates the activable pool of nAChRs. We performed fluorescent recovery after photobleaching (FRAP), quantitative RT-PCR, and whole cell patch clamp recordings of GFP-encoding Mus musculus nAChRs transfected into HEK 293 cells to assess the role of cholesterol and caveolin-1 (CAV-1) in the diffusion, expression, and functionality of the nAChR (WT and αC418W). Our findings support the hypothesis that a cholesterol-sensitive nAChR might reside in specialized membrane microdomains that upon cholesterol depletion become disrupted and release the cholesterol-sensitive nAChRs to the pool of activable receptors. In addition, our results in HEK 293 cells show an interdependence between CAV-1 and αC418W that could confer end plates rich in αC418W nAChRs to a susceptibility to changes in cholesterol levels that could cause adverse drug reactions to cholesterol-lowering drugs such as statins. The current work suggests that the interplay between cholesterol and CAV-1 provides the molecular basis for modulating the function and dynamics of the cholesterol-sensitive αC418W nAChR.

Generalizing thermodynamic properties of bulk single-walled carbon nanotubes.

The enthalpy and Gibbs free energy thermodynamical potentials of single walled carbon nanotubes were studied of all types (armchairs, zig-zags, chirals (n>m), and chiral (n

Combining geometrical and dynamical disorder to enhance transport.

We look for the optimal way to distribute rectifiers in order to maximize their effect on the transport properties of Brownian particles. These rectifiers are introduced in the form of flashing asymmetric potentials distributed on a one dimensional lattice. We study the effects that different distributions of these rectifiers have on the generated current and on the energy cost of transport. Based on both analytical and numerical results, we observe an unexpected increase in the efficiency of the rectifiers and the magnitude of the current for the case in which geometrical and dynamical disorder are combined. We show that this effect is a direct consequence of the "hitchhiker" or "waiting time" paradox.

Combined effect of periodic gates and external fields on the diffusion coefficient of a single particle.

A general analytical expression to describe the diffusion of a single particle in a one-dimensional lattice with periodically distributed gates of lifetime (tau) and while under the influence of a constant external field is calculated. A formulation based on a microscopic model and a diffusion relaxation condition is used to derive an equation for the diffusion coefficient as a function of the concentration of gates (c), the lifetime (tau) of such gates, and the strength of the external field (p). The theory is compared against Monte Carlo simulations, and limiting cases are used to reproduce previously published results on a variety of phenomena.

Engineering reactions in crystalline solids: predicting photochemical decarbonylation from calculated thermochemical parameters.

A detailed thermochemical analysis of the alpha-cleavage and decarbonylation reactions of acetone and several ketodiesters was carried out with the B3LYP/6-31G* density functional method. The heats of formation of several ground-state ketones and radicals were calculated at 298 K to determine bond dissociation energies (BDE) and radical stabilization energies (RSE) as a function of substituents. Results show that the radical-stabilizing abilities of the ketone substituents play a very important role on the thermodynamics of the alpha-cleavage and decarbonylation steps. An excellent correlation between calculated values and previous experimental observations suggests that photochemical alpha-cleavage and decarbonylation in crystals should be predictable from knowledge of excitation energies and the RSE of the substituent.