What Can We Learn about Cholesterol's Transmembrane Distribution Based on Cholesterol-Induced Changes in Membrane Dipole Potential?

Cholesterol is abundant in the plasma membranes of animal cells and is known to regulate a variety of membrane properties. Despite decades of research, the transmembrane distribution of cholesterol is still a matter of debate. Here we consider this outstanding issue through atomistic simulations of asymmetric lipid membranes, whose composition is largely consistent with eukaryotic plasma membranes. We show that the membrane dipole potential changes in a cholesterol-dependent manner. Remarkably, moving cholesterol from the extracellular to the cytosolic leaflet increases the dipole potential on the cytosolic side, and vice versa. Biologically this implies that by altering the dipole potential, cholesterol can provide a driving force for cholesterol molecules to favor the cytosolic leaflet, in order to compensate for the intramembrane field that arises from the resting potential.

Molecular dynamics simulation of spin-lattice NMR relaxation in poly-L-lysine dendrimers: manifestation of the semiflexibility effect.

NMR relaxation experiments are widely used to investigate the local orientation mobility in dendrimers. In particular, the NMR method allows one to measure the spin-lattice relaxation rate, 1/T1, which is connected with the orientational autocorrelation function (ACF) of NMR active groups. We calculate the temperature (Θ) and frequency (ω) dependences of the spin-lattice NMR relaxation rates for segments and NMR active CH2 groups in poly-L-lysine (PLL) dendrimers in water, on the basis of full-atomic molecular dynamics simulations. It is shown that the position of the maximum of 1/T1(ω) depends on the location of the segments inside the dendrimer. This dependence of the maximum is explained by the restricted flexibility of the dendrimer. Such behavior has been predicted recently by the analytical theory based on the semiflexible viscoelastic model. The simulated temperature dependences of 1/T1 for terminal and inner groups in PLL dendrimers of n = 2 and n = 4 generations dissolved in water are in good agreement with the NMR experimental data, which have been obtained for these systems previously by us. It is shown that in the case of PLL dendrimers, the traditional procedure of the interpretation of NMR experimental data - when smaller values of 1/T1 correspond to higher orientation mobility - is applicable to the whole accessible frequency interval only for the terminal groups. For the inner groups, this procedure is valid only at low frequencies.

Thermal properties of bulk polyimides: insights from computer modeling versus experiment.

Due to the great importance for many industrial applications it is crucial from the point of view of theoretical description to reproduce thermal properties of thermoplastic polyimides as accurate as possible in order to establish "chemical structure-physical properties" relationships of new materials. In this paper we employ differential scanning calorimetry, dilatometry, and atomistic molecular dynamics (MD) simulations to explore whether the state-of-the-art computer modeling can serve as a precise tool for probing thermal properties of polyimides with highly polar groups. For this purpose the polyimide R-BAPS based on dianhydride 1,3-bis(3',4-dicarboxyphenoxy)benzene (dianhydride R) and diamine 4,4'-bis(4''-aminophenoxy)biphenyl sulphone) (diamine BAPS) was synthesized and extensively studied. Overall, our findings show that the widely used glass-transition temperature Tg evaluated from MD simulations should be employed with great caution for verification of the polyimide computational models against experimental data: in addition to the well-known impact of the cooling rate on the glass-transition temperature, correct definition of Tg requires cooling that starts from very high temperatures (no less than 800 K for considered polyimides) and accurate evaluation of the appropriate cooling rate, otherwise the errors in the measured values of Tg become undefined. In contrast to the glass-transition temperature, the volumetric coefficient of thermal expansion (CTE) does not depend on the cooling rate in the low-temperature domain (T < Tg) so that comparison of computational and experimental values of CTE provides a much safer way for proper validation of the theoretical model when electrostatic interactions are taken into account explicitly. Remarkably, this conclusion is most likely of generic nature: we show that it also holds for the commercial polyimide EXTEM, another polyimide with a similar chemical structure.