Simulating Bilayers of Nonionic Surfactants with the GROMOS-Compatible 2016H66 Force Field.

Polyoxyethylene glycol alkyl ether amphiphiles (CiEj) are important nonionic surfactants, often used for biophysical and membrane protein studies. In this work, we extensively test the GROMOS-compatible 2016H66 force field in molecular dynamics simulations involving the lamellar phase of a series of CiEj surfactants, namely C12E2, C12E3, C12E4, C12E5, and C14E4. The simulations reproduce qualitatively well the monitored structural properties and their experimental trends along the surfactant series, although some discrepancies remain, in particular in terms of the area per surfactant, the equilibrium phase of C12E5, and the order parameters of C12E3, C12E4, and C12E5. The polar head of the CiEj surfactants is highly hydrated, almost like a single polyethyleneoxide (PEO) molecule at full hydration, resulting in very compact conformations. Within the bilayer, all CiEj surfactants flip-flop spontaneously within tens of nanoseconds. Water-permeation is facilitated, and the bending rigidity is 4 to 5 times lower than that of typical phospholipid bilayers. In line with another recent theoretical study, the simulations show that the lamellar phase of CiEj contains large hydrophilic pores. These pores should be abundant in order to reproduce the comparatively low NMR order parameters. We show that their contour length is directly correlated to the order parameters, and we estimate that they should occupy approximately 7-10% of the total membrane area. Due to their highly dynamic nature (rapid flip-flops, high water permeability, observed pore formation), CiEj surfactant bilayers are found to represent surprisingly challenging systems in terms of modeling. Given this difficulty, the results presented here show that the 2016H66 parameters, optimized independently considering pure-liquid as well as polar and nonpolar solvation properties of small organic molecules, represent a good starting point for simulating these systems.

Optimizing an ultrasound contrast agent's stability using in vitro attenuation measurements.

RATIONALE AND OBJECTIVES: To evaluate the changes in the microbubble population of a currently available ultrasound contrast agent (USCA) through attenuation measurements to optimize its clinical use. MATERIALS AND METHODS: The microbubble population from a galactose-based USCA (Levovist, Schering AG, Germany) was characterized in vitro using attenuation measurements. The effect of dose (0.1, 0.5, and 1 mL), concentrations (200, 300, and 400 mg mL(-1)) and time since reconstitution (2, 12, 22, and 32 minutes) was evaluated using two broadband pulses at different peak negative pressures (0.39 and 0.49 MPa) for a total of 72 injections. RESULTS: Two minutes after reconstitution, a linear relationship was found between attenuation measurements and the amount of USCA (slope 0.92 dB x mg x cm(-1) ml(-1), R = 0.86). For a given dose and concentration, the microbubble stability was significantly reduced with the increase of the time since reconstitution, particularly for the lower concentrations. CONCLUSIONS: The persistence and contrast effect of Levovist can be improved by using recommended minimum time since reconstitution and maximum concentration.

Molecular origin of model membrane bending rigidity.

The behavior of the bending modulus kappa of bilayers in lamellar phases was studied by Small Angle X-ray Scattering technique for various nonionic C(i)E(j) surfactants. The bilayers are either unswollen and dispersed in water or swollen by water and dispersed in dodecane. For unswollen bilayers, the values of kappa decrease with both an increase in the area per surfactant molecule and in the polar head length. They increase when the aliphatic chain length increases at constant area per surfactant molecule. Whereas for water-swollen membranes, the values of kappa decrease as the content of water increases converging to the value of the single monolayer bending modulus. Such a behavior results from the decoupling of the fluctuations of the two surfactant membrane monolayers. Our results emphasize the determinant contribution of the surfactant conformation to kappa.

Blood flow quantification with contrast-enhanced US: "entrance in the section" phenomenon--phantom and rabbit study.

PURPOSE: To investigate changes in destruction-replenishment curves (in vitro and in vivo) that result from microbubble destruction in feeding vessels that pass through the imaging plane before microbubbles enter the region of interest (ROI). MATERIALS AND METHODS: During continuous injections of an ultrasonographic contrast agent, nonlinear gray-scale images were obtained in vitro in the longitudinal plane of a renal dialysis cartridge flow phantom (flow rates of 100, 200, and 400 mL/min) and in vivo in the coronal plane of the left kidneys of two rabbits (two kidneys). Destruction-replenishment curves were obtained for the dialysis cartridge in ROIs located immediately after the entrance of the microbubbles into the image plane and further from the entrance, after microbubbles had traveled across the complete length of the imaging plane. Replenishment curves were also obtained from ROIs in the rabbit kidneys at the level of segmental arteries, distal interlobar arteries, and the cortex. RESULTS: The ROIs immediately after the entrance of the microbubbles in the image plane of the dialysis cartridge and in the segmental artery of the kidney followed a typical exponential function, A(1 - e-alphat). Early portions of curves obtained in ROIs filled with microbubbles that had already passed through the image plane of the dialysis cartridge or in the renal cortex were not well described by such a function. The shape of the curve and the variations as a function of flow rate can be explained by means of a mathematical model based on indicator-dilution theory. CONCLUSION: When the feeding vessels of an ROI travel across the ultrasound field before they reach the measurement region, the typical shape of the replenishment curve is modified (reduced velocity parameter and plateau).