Medical contrast media as possible tools for SAXS contrast variation

Abstract

Small-angle X-ray scattering (SAXS) is increasingly used to extract structural information from a multitude of soft-matter and biological systems in aqueous solution, including polymers, detergents, lipids, colloids, proteins and RNA/DNA. When SAXS data are recorded at multiple contrasts, i.e. at different electron densities of the solvent, the internal electron-density profile of solubilized molecular systems can be probed. However, contrast-variation SAXS has been limited by the range of electron densities available by conventional agents such as sugars, glycerol and salt, and by the fact that many soft-matter and biological systems are modified in their presence. Here we present a pioneering SAXS contrast-variation study on DDM (n-dodecyl-β-D-maltopyranoside) micelles by using two highly electron-rich contrast agents from biomedical imaging which belong to the families of gadolinium-based and iodinated molecules. The two agents, Gd-HPDO3A and iohexol, were allowed to attain modifications of the solvent electron density that are 50 to 100% higher than those obtained for sucrose, and are located between the electron densities of proteins and RNA/DNA. In the case of Gd-HPDO3A, an analysis of the internal micellar structure was possible and compared with results obtained with sucrose. In conclusion, medical contrast agents represent a promising class of molecules for SAXS contrast-variation experiments with potential applications for numerous soft-matter and biological systems, including membrane proteins and protein–RNA/DNA complexes.

Lipid Hydroperoxide Compromises the Membrane Structure Organization and Softens Bending Rigidity

“…P t ( q ) contains information about the lipid bilayer structure and it is here modeled as step functions with three different electron densities (ρ) in respect to the electron density of the buffer (ρ buf = 0.34(2) e/Å 3 ). , These regions are characterized by their electron densities ρ and thicknesses R from the center of the bilayer toward the aqueous solution as (i) a methyl region (ρ CH3 , R CH3 ), (ii) a CH 2 chains-containing inner lipid bilayer medium (ρ CH2 , R CH2 ), and (iii) an outer membrane containing polar headgroups and solvation molecules (ρ pol , R pol ): with …”

Small-Angle X-ray Scattering Curves of Detergent Micelles: Effects of Asymmetry, Shape Fluctuations, Disorder, and Atomic Details

“…To investigate the structural information in SAXS curves of soft-matter complexes, we measured the SAXS curve of a n -dodecyl-β- d -maltoside (DDM) detergent micelle up to q = 6 nm –1 , where q = 4π sin­(θ)/λ with the X-ray wavelength λ and the scattering angle 2θ. Using a recently developed method for coupling parallel-replica MD simulations to experimental SAXS data, we refined a heterogeneous atomic ensemble against the data with commitment to the principle of maximum entropy. , Having the atomistic ensemble in agreement with the data as a reference, we deciphered step-by-step the influence of model symmetry, shape fluctuations, disorder, and atomic detail on the SAXS curve, by comparing the results from MD simulations with the results obtained using simplified micelle models.…”

Altering the X-ray Scattering Contrast of Triton X-100 Micelles and Its Trapping in a Supercooled Solvent

“…The ability of this mixture in sustaining self-assembly is advantageous as it can be used as an additive to vary the solvent electron density for SAXS characterization. Recently there have been attempts to use commercial MRI contrast agents as additives to alter the electron density of solvent and hence resolve the structure of micelles in water …”

“…Recently there have been attempts to use commercial MRI contrast agents as additives to alter the electron density of solvent and hence resolve the structure of micelles in water. 49…”