Abstract
The mechanical properties of multilayer stacks of Gb3 glycolipid that play key roles in metabolic disorders (Fabry disease) were determined quantitatively by using specular and off-specular neutron scattering. Because of the geometry of membrane stacks deposited on planar substrates, the scattered intensity profile was analyzed in a 2D reciprocal space map as a function of in-plane and out-of-plane scattering vector components. The two principal mechanical parameters of the membranes, namely, bending rigidity and compression modulus, can be quantified by full calculation of scattering functions with the aid of an effective cut-off radius that takes the finite sample size into consideration. The bulkier "bent" Gb3 trisaccharide group makes the membrane mechanics distinctly different from cylindrical disaccharide (lactose) head groups and shorter "bent" disaccharide (gentiobiose) head groups. The mechanical characterization of membranes enriched with complex glycolipids has high importance in understanding the mechanisms of diseases such as sphingolipidoses caused by the accumulation of non-degenerated glycosphingolipids in lysosomes or inhibition of protein synthesis triggered by the specific binding of Shiga toxin to Gb3.
Highlights
X-ray and neutron scattering1–5 from isotropic lipid suspensions have been widely used to gain insight into structural features of biological membranes over multiple length scales as a function of temperature,6,7 osmotic pressure,8,9 and the molar ratios of substitutional additives.1,10 powder diffraction experiments do not allow for the discrimination of momentum transfers parallel and perpendicular to the membrane planes
Because of the geometry of membrane stacks deposited on planar substrates, the scattered intensity profile was analyzed in a 2D reciprocal space map as a function of in-plane and out-of-plane scattering vector components
We physically model the impact of glycolipid on the membrane mechanics which leads to human diseases, such as toxin uptake and metabolic disorders
Summary
X-ray and neutron scattering from isotropic lipid suspensions have been widely used to gain insight into structural features of biological membranes over multiple length scales as a function of temperature, osmotic pressure, and the molar ratios of substitutional additives (cholesterol, proteins, etc.). powder diffraction experiments do not allow for the discrimination of momentum transfers parallel and perpendicular to the membrane planes. X-ray and neutron scattering from isotropic lipid suspensions have been widely used to gain insight into structural features of biological membranes over multiple length scales as a function of temperature, osmotic pressure, and the molar ratios of substitutional additives (cholesterol, proteins, etc.).. Specular signals reflect the inter-membrane potentials between neighboring membranes, while off-specular signals reflect intramembrane structural order, such as pores formed by peptides.. Specular signals reflect the inter-membrane potentials between neighboring membranes, while off-specular signals reflect intramembrane structural order, such as pores formed by peptides.13,14 In this account, we physically model the impact of glycolipid on the membrane mechanics which leads to human diseases, such as toxin uptake and metabolic disorders. As a model of glycolipid, we synthesized a lipid with a globotriaose (α-galactose(1-4)-β-galactose(1-4)-β-glucose, Gb3) head group.
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