Influence of Ca2+ on the surface behavior of phosphatidic acid and its mixture with diacylglycerol pyrophosphate at different pHs

Margutti, Micaela Peppino; Wilke, Natalia; Villasuso, Ana Laura

doi:10.1016/j.chemphyslip.2020.104887

Cited by 5 publications

(6 citation statements)

References 37 publications

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“…The interaction of Ca

with anionic lipids such as phosphatidic acid and its derivative diacylglycerol pyrophosphate, which are in turn involved in signaling pathways themselves, is characterized by lipid clustering and membrane stiffening, as demonstrated using Langmuir films [ 70 ]. Ca

binding interacts in an 1:1 stoichiometry with singly-charged di-basic phosphatidic acid, decreasing the second acidic pKa and forming a neutral lipid:Ca(II) complex [ 71 ].…”

Section: Effects Of Ions Different From Protonsmentioning

confidence: 99%

On the Coupling between Mechanical Properties and Electrostatics in Biological Membranes

Galassi

Wilke

2021

Membranes

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Cell membrane structure is proposed as a lipid matrix with embedded proteins, and thus, their emerging mechanical and electrostatic properties are commanded by lipid behavior and their interconnection with the included and absorbed proteins, cytoskeleton, extracellular matrix and ionic media. Structures formed by lipids are soft, dynamic and viscoelastic, and their properties depend on the lipid composition and on the general conditions, such as temperature, pH, ionic strength and electrostatic potentials. The dielectric constant of the apolar region of the lipid bilayer contrasts with that of the polar region, which also differs from the aqueous milieu, and these changes happen in the nanometer scale. Besides, an important percentage of the lipids are anionic, and the rest are dipoles or higher multipoles, and the polar regions are highly hydrated, with these water molecules forming an active part of the membrane. Therefore, electric fields (both, internal and external) affects membrane thickness, density, tension and curvature, and conversely, mechanical deformations modify membrane electrostatics. As a consequence, interfacial electrostatics appears as a highly important parameter, affecting the membrane properties in general and mechanical features in particular. In this review we focus on the electromechanical behavior of lipid and cell membranes, the physicochemical origin and the biological implications, with emphasis in signal propagation in nerve cells.

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“…The interaction of Ca

binding interacts in an 1:1 stoichiometry with singly-charged di-basic phosphatidic acid, decreasing the second acidic pKa and forming a neutral lipid:Ca(II) complex [ 71 ].…”

Section: Effects Of Ions Different From Protonsmentioning

confidence: 99%

On the Coupling between Mechanical Properties and Electrostatics in Biological Membranes

Galassi

Wilke

2021

Membranes

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“…An unanswered question is how PA and DGPP interact when present in the same bilayer leaflet. Monolayer work suggests that PA and DGPP may form domains [ 19 ] but this needs to be corroborated in model lipid bilayers. It is tempting to speculate however that fine tuning of the concentration of PA and DGPP in a given membrane may thus be one mechanism by which to sensitively control PA—Protein interactions and lipid signaling.…”

Section: Discussionmentioning

confidence: 99%

“…After conversion of PA to DGPP [ 10 ], a DGPP enriched biomembrane will have less negative curvature stress and an increased negative surface potential, which is likely to influence the interaction with (cationic) ions and proteins [ 17 ]. However, the interaction of DGPP with cationic amino acids and/or divalent cations has not been fully explored and is the main focus of this work [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…As seen in PI(4,5)P 2 , phosphate position and orientation together with the inherent properties of these divalent cations affect their binding. Margutti et al showed that calcium affected the surface pressure of DGPP (containing) monolayers differentially at pH 5 and 8 using Langmuir monolayers [ 19 ]. No literature exists on the interaction of Mg 2+ with DGPP and how this compares with Ca 2+ .…”

Section: Introductionmentioning

confidence: 99%

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The Electrostatic Basis of Diacylglycerol Pyrophosphate—Protein Interaction

Graber

Kwarteng

Lange

et al. 2022

Cells

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Diacylglycerol pyrophosphate (DGPP) is an anionic phospholipid formed in plants, yeast, and parasites under multiple stress stimuli. It is synthesized by the phosphorylation action of phosphatidic acid (PA) kinase on phosphatidic acid, a signaling lipid with multifunctional properties. PA functions in the membrane through the interaction of its negatively charged phosphomonoester headgroup with positively charged proteins and ions. DGPP, like PA, can interact electrostatically via the electrostatic-hydrogen bond switch mechanism but differs from PA in its overall charge and shape. The formation of DGPP from PA alters the physicochemical properties as well as the structural dynamics of the membrane. This potentially impacts the molecular and ionic binding of cationic proteins and ions with the DGPP enriched membrane. However, the results of these important interactions in the stress response and in DGPP’s overall intracellular function is unknown. Here, using 31P MAS NMR, we analyze the effect of the interaction of low DGPP concentrations in model membranes with the peptides KALP23 and WALP23, which are flanked by positively charged Lysine and neutral Tryptophan residues, respectively. Our results show a significant effect of KALP23 on the charge of DGPP as compared to WALP23. There was, however, no significant effect on the charge of the phosphomonoester of DGPP due to the interaction with positively charged lipids, dioleoyl trimethylammonium propane (DOTAP) and dioleoyl ethyl-phosphatidylcholine (EtPC). Divalent calcium and magnesium cations induce deprotonation of the DGPP headgroup but showed no noticeable differences on DGPP’s charge. Our results lead to a novel model for DGPP—protein interaction.

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“…Prior studies on impact of charged lipids on membrane phase behavior have heavily focused on anionic lipids, PG and PS, perhaps due to the prominent role of these lipids in biological membranes. − Here, we decided to explore both anionic and cationic lipids as cationic lipids have also found growing application in liposomal delivery systems and have even been explored for use in phase-separating membranes. − For anionic lipid, we focused on DOPA as PA is known for its key role in cell signaling and lipid metabolism and as an important precursor for biosynthesis of other lipids . For cationic lipid, we selected DOTAP due to its wide application in fusogenic liposomes and delivery of nucleic acids. − Both DOPA and DOTAP have acyl-chains similar to DOPC and were therefore used to replace DOPC in the examined DOPC:DPPC:Chol membranes assuming that they would have similar phase partitioning behavior as DOPC.…”

Section: Introductionmentioning

confidence: 99%

Charged Lipids Modulate the Phase Separation in Multicomponent Membranes

Wang

Majd

2023

Langmuir

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Phase separation in lipid membranes controls the organization of membrane components and thus regulates membrane-mediated processes. Membrane phase behavior is influenced by the molecular properties of its components and their relative concentrations. Charged lipid species are among the most essential components of lipid membranes, and their impact on the membrane phase behavior is yet to be fully understood. Aiming to provide insight into this impact, this paper investigates how the presence and amount of anionic and cationic lipids affect the phase behavior of multicomponent membranes. Membranes of ternary composition DOPC:DPPC:Chol with two distinct molar ratios were used to test the hypothesis that inclusion of charged lipids with saturated tails, beyond a certain concentration, would impede phase separation in an otherwise phase-separating membrane. Fluorescence microscopy examination of electroformed giant liposomes revealed that when more than half of DOPC in the examined mixtures was replaced with DOPA or DOTAP, phase separation in liposomes was somewhat suppressed, and this effect increased with increasing charged lipid content. This effect depended on the membrane surface charge density as the half-maximal effect was observed at around 0.0072 C Å −2 in all examined cases. The phase-separation suppressing effect of DOPA was neutralized when oppositely charged lipid DOTAP was included in the mixture. Likewise, presence of divalent cation Ca 2+ in the solution neutralized the impact of negatively charged DOPA. These results underline the detrimental influence of surface charge density on membrane phase behavior. More importantly, these findings suggest that the charged lipid content in membranes may be a regulator of their phase behavior and open new opportunities for the design of synthetic lipid membranes.

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Influence of Ca2+ on the surface behavior of phosphatidic acid and its mixture with diacylglycerol pyrophosphate at different pHs

Cited by 5 publications

References 37 publications

On the Coupling between Mechanical Properties and Electrostatics in Biological Membranes

On the Coupling between Mechanical Properties and Electrostatics in Biological Membranes

The Electrostatic Basis of Diacylglycerol Pyrophosphate—Protein Interaction

Charged Lipids Modulate the Phase Separation in Multicomponent Membranes

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