Lipid Membrane State Change by Catalytic Protonation and the Implications for Synaptic Transmission

In cholinergic synapses, the neurotransmitter acetylcholine (ACh) is rapidly hydrolyzed by esterases to choline and acetic acid (AH). It is believed that this reaction serves the purpose of deactivating ACh once it has exerted its effect on a receptor protein (AChR). The protons liberated in this reaction, however, may by themselves excite the postsynaptic membrane. Herein, we investigated the response of cell membrane models made from phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidic acid (PA) to ACh in the presence and absence of acetylcholinesterase (AChE). Without a catalyst, there were no significant effects of ACh on the membrane state (lateral pressure change ≤0.5 mN/m). In contrast, strong responses were observed in membranes made from PS and PA when ACh was applied in presence of AChE (>5 mN/m). Control experiments demonstrated that this effect was due to the protonation of lipid headgroups, which is maximal at the pK (for PS: pKCOOH≈5.0; for PA: pKHPO4−≈8.5). These findings are physiologically relevant, because both of these lipids are present in postsynaptic membranes. Furthermore, we discussed evidence which suggests that AChR assembles a lipid-protein interface that is proton-sensitive in the vicinity of pH 7.5. Such a membrane could be excited by hydrolysis of micromolar amounts of ACh. Based on these results, we proposed that cholinergic transmission is due to postsynaptic membrane protonation. Our model will be falsified if cholinergic membranes do not respond to acidification.

Impact of Material Stiffness and Anisotropy on Coaptation Characteristics for Aortic Valve Cusps Reconstructed from Pericardium

The numerical assessment of reconstructed aortic valves competence and leaflet design optimization rely on both coaptation characteristics and the diastolic valve configuration. These characteristics can be evaluated by the shell or membrane formulations. The membrane formulation is preferable for surgical aortic valve neocuspidization planning since it is easy to solve. The results on coaptation zone sensitivity to the anisotropy of aortic leaflet material are contradictive, and there are no comparisons of coaptation characteristics based on shell and membrane models for anisotropic materials. In our study, we explore for the first time how the reduced model and anisotropy of the leaflet material affect the coaptation zone and the diastolic configuration of the aortic valve. To this end, we propose the method to mimic the real, sutured neo-leaflet, and apply our numerical shell and membrane formulations to model the aortic valve under the quasi-static diastolic pressure varying material stiffness and anisotropy directions. The shell formulation usually provides a lesser coaptation zone than the membrane formulation, especially in the central zone. The material stiffness does influence the coaptation zone: it is smaller for stiffer material. Anisotropy of the leaflet material does not affect significantly the coaptation characteristics, but can impact the deformed leaflet configuration and produce a smaller displacement.

Molecular dynamics simulation of a model brain membrane with and without a 14-3-3 tau protein

An unbalanced composition of lipids and proteins in brain membranes is related to the appearance neurodegenrative diseases and recent investigations show that the 14-3-3 tau protein might relate to some of these diseases. This article reports results from a coarse-grained model brain membrane with and without a 14-3-3 τ/θ protein inside the membrane. We investigated the symmetrized partial density, thickness, diffusion coefficients, and deuterium order parameters of the membrane with and without protein. We observe a slight increase in heads and linkers in the symmetrized partial density of the membrane with the protein inserted and higher values of the deuterium order parameters for the brain model membrane with protein. We observe a reduction in the diffusion coefficient of the fluid membrane in the presence of the transmembrane tau protein. Our findings show that the protein can modify the structural and dynamical properties of the membrane. This work will serve as a guide for future investigations on the interactions of tau proteins with brain membrane models and their relation to neurodegenerative diseases.