Ceramide increases free volume voids in DPPC membranes

Abstract

Positron annihilation lifetime spectroscopy (PALS) can measure changes in local free volume voids in lipid bilayers. PALS has been applied, together with differential scanning calorimetry (DSC) and molecular dynamics (MD) simulations, to study free volume voids in DPPC and DPPC:ceramide (85:15 mol:mol) model membranes in the 20-60 ºC range. The free volume void average size clearly increases with the gel-fluid phase transition of the lipid, or lipid mixture. Ceramide increases void size at all temperatures, particularly in the range causing the gel-fluid transition of the mixture. A parallel study of PALS and calorimetric data indicates that, for the complex thermotropic transition of the DPPC:ceramide mixture, PALS is detecting the transition of the DPPC component, while calorimetry changes indicate mainly the melting of the ceramide-enriched domains. Molecular dynamics calculations provide a clear distinction between ceramide-rich and -poor domains, and show that the voids are predominantly located near the membrane nodal plane. The ceramide-induced increase in void volume size occurs as well at temperatures when both phospholipid and ceramide are in the fluid state, indicating that the effect is not the result of phospholipid-ceramide domain coexistence. The above observations may be related to hitherto unexplained properties of ceramide, such as the increase in membrane permeability, and the induction of transmembrane (flip-flop) lipid motion.

A Multiscale Model for Solute Diffusion in Hydrogels

“…In this work we made use of the Gaussian error function, which is classically encountered in many problems in diffusion, as the prefactor. It is well-known that the radius of the free volume holes in many hydrogels and diverse biological tissues follow a Gaussian distribution with an average r FV and a distribution breadth denoted by σ VF . − For a particle with radius r s and free volume holes of r FV that are normally distributed, the corresponding error function is . This function describes the probability that a diffusing particle of r s will find a single intermolecular space of r FV , which falls in the range of 0–1 since is always a positive value.…”

Ceramide-Induced Lamellar Gel Phases in Fluid Cell Lipid Extracts

“…Nanoindentation curves reveal a single pattern (thus confirming the homogeneity of the sample) with F b = 2.49 ± 0.68 nN (Figure a, Table ). This nanomechanical resistance would be too weak for a standard gel phase ,,, but would be within the range of a liquid-disordered phase. , The possibility of a liquid-ordered (L o ) phase cannot be underestimated as the Chol content is so high, but the observed nanomechanical resistance would be too low for an L o phase. Among the liquid-ordered phases studied in previous reports, such as 7:3 pSM:Chol and 7:3 DPPC:Chol mole ratios, , main F b values were in the range of ∼20 nN or higher, and other reports point to other L o phases with nanomechanical resistance in the range of 10 nN .…”

“…Although for many decades they were considered merely structural elements, some years ago with the discovery of the sphingolipid signaling pathway − the interest in these lipids was renewed and very soon ceramide, sphingosine, and other related compounds became established as lipid second messengers or metabolic signals. Long-chain ceramides (>14 carbons in the N -acyl chain) have been related to cell death, , and they are known to cause drastic changes in the biophysical properties of the membranes, enhancing flip-flop motion, solute efflux, , free volume void size increase, and domain segregation . Ceramide-enriched domains have also been described in red blood cells and mitochondrial outer membranes .…”

Lipid Self-Assemblies under the Atomic Force Microscope

“…Over the last decade, molecular dynamics simulations have also gained relevance in the field [47,79,80], and, as the lipid membrane concept is extremely plastic and the bilayer can also be interpreted as a biomaterial, the field is also open for other techniques from different physics-related fields. Thus, techniques such as positron annihilation lifetime spectroscopy have been applied successfully to membrane characterization [81,82]. Another physical tool that has acquired great predominance in the field is atomic force microscopy (AFM) [83], which is a kind of multi-purpose scanning probe microscopy conceptually derived from the scanning tunnel microscopy (STM), but with great advantages for biological applications, the most important ones being the possibility of scanning aqueous samples [84] and the capacity for non-charged sample scanning.…”