arXiv subjects

Fabian Keller

Publications and source records attributed to Fabian Keller.

4 recordsLinked to original sources

arXiv2022

A mechanistic perspective on the effect of cholesterol in phospholipid bilayers

Cholesterol (CHOL) is one of the most important components of plasma membranes of higher cells and one of the main factors for the formation of (nano)domains. In this work, molecular dynamics simulations of mixtures of CHOL with DPPC (saturated lipid) and DLiPC (unsaturated lipid) as standard phospholipids (PLs) are presented in a wide range of CHOL concentrations. The key idea is to systematically extract all structural and enthalpic properties relevant to the formulation of a lattice model of these systems and express them in dependence of the acyl chain order parameters. Detailed interpretation is simplified by the observation that, to a good approximation, the interaction effects do not depend on the total CHOL concentration, but only on the local CHOL arrangement. The resulting information can be used to motivate the agglomeration of CHOL molecules, the relevance of entropic rather than enthalpic effects for understanding the stronger influence of CHOL on DPPC compared to DLiPC, or the thermodynamic background of raft formation. It is verified that the interaction functions hardly change during the transition from binary to ternary mixtures, suggesting the applicability of the concepts to more complex mixtures.

physics.bio-ph↗

arXiv2021

Effect of Cholesterol vs. Ergosterol on DPPC Bilayer Properties: Insights from Atomistic Simulations

Sterols have been ascribed a major role in the organization of biological membranes, in particular for the formation of liquid ordered domains in complex lipid mixtures. Here, we employed molecular dynamics simulations to compare the effects of cholesterol and ergosterol as the major sterol of mammalian and fungal cells, respectively, on binary mixtures with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as a proxy for saturated lipids. In agreement with previous work, we observe that the addition of sterol molecules modifies the order of DPPC both in the gel phase and in the liquid phase. When disentangling the overall tilt angle and the structure of the tail imposed by trans/gauche configurations of torsion angles in the tail, respectively, a more detailed picture of the impact of sterols can be formulated, revealing, e.g., an approximate temperature-concentration superposition ranging from the liquid to the gel phase. Furthermore, a new quantitative measure to identify the presence of collective sterol effects is discussed. Moreover, when comparing both types of sterols, addition of cholesterol has a noticeably stronger impact on phospholipid properties than of ergosterol. The observed differences can be attributed to higher planarity of the cholesterol ring system. This planarity combined with an inherent asymmetry in its molecular interactions leads to better alignment and hence stronger interaction with saturated acyl chains. Our results suggest that the high order demonstrated for ergosterol in fungal plasma membranes must therefore be generated via additional mechanisms.

physics.bio-ph↗

arXiv2021

Chain ordering of phospholipids in membranes containing cholesterol: What matters?

Cholesterol (CHOL) drives lipid segregation and is thus a key player for the formation of lipid rafts and followingly for the ability of a cell to, e.g., enable selective agglomeration of proteins. The lipid segregation is driven by cholesterol's affinity for saturated lipids, which stands directly in relation to the ability of cholesterol to order the individual phospholipid (PL) acyl chains. In this work, Molecular Dynamics simulations of DPPC (Dipalmitoylphosphatidylcholine, saturated lipid) and DLiPC (Dilineoylphosphatidylcholine, unsaturated lipid) mixtures with cholesterol are used to elucidate the underlying mechanisms of the cholesterol ordering effect. To this end, all enthalpic contributions, experienced by the PL molecules, are recorded as a function of the PL's acyl chain order. This involves, the PL-PL, the PL-cholesterol interaction, the interaction of the PLs with water, and the interleaflet interaction. This systematic analysis allows one to unravel differences of saturated and unsaturated lipids in terms of the different interaction factors. It turns out that cholesterol's impact on chain ordering stems not only from direct interactions with the PLs but is also indirectly present in the other energy contributions. Furthermore, the analysis sheds light on the relevance of the entropic contributions, related to the degrees of freedom of the acyl chain.

physics.bio-ph↗

arXiv2011

A Hierarchical NeuroBayes-based Algorithm for Full Reconstruction of B Mesons at B Factories

We describe a new B-meson full reconstruction algorithm designed for the Belle experiment at the B-factory KEKB, an asymmetric e+e- collider that collected a data sample of 771.6 x 10^6 BBbar pairs during its running time. To maximize the number of reconstructed B decay channels, it utilizes a hierarchical reconstruction procedure and probabilistic calculus instead of classical selection cuts. The multivariate analysis package NeuroBayes was used extensively to hold the balance between highest possible efficiency, robustness and acceptable consumption of CPU time. In total, 1104 exclusive decay channels were reconstructed, employing 71 neural networks altogether. Overall, we correctly reconstruct one B+/- or B0 candidate in 0.28% or 0.18% of the BBbar events, respectively. Compared to the cut-based classical reconstruction algorithm used at the Belle experiment, this is an improvement in efficiency by roughly a factor of 2, depending on the analysis considered. The new framework also features the ability to choose the desired purity or efficiency of the fully reconstructed sample freely. If the same purity as for the classical full reconstruction code is desired ~25%, the efficiency is still larger by nearly a factor of 2. If, on the other hand, the efficiency is chosen at a similar level as the classical full reconstruction, the purity rises from ~25% to nearly 90%.

hep-ex↗