The degree and position of phosphorylation determine the impact of toxic and trace metals on phosphoinositide containing model membranes

Daear, Weiam; Mundle, Robyn; Sule, Kevin; Prenner, Elmar J.

doi:10.1016/j.bbadva.2021.100021

Cited by 8 publications

(10 citation statements)

References 105 publications

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“…The strong dependence on lipid head group and side chain structure allows differential localized effects within a cell, between cell types and upon metabolically induced changes in lipid composition. These consequences and others reported metal effects in the literature, such as PA charge changes and altered membrane domain formation for phosphoinositides, may have profound effects on proper cellular functions [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Both PA and PS were attractive targets for Mn, which exuded a relatively stronger impact on membrane fluidity and liposome size, compared to Ca and Mg. Mn binding to anionic phospholipid membranes has been reported, resulting in increased membrane rigidity, permeability and aggregation [ 17 , 29 , 51 ]. Moreover, Mn interaction with POPA and DMPA revealed strong membrane rigidification, liposome size increases and shifts in T m [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…Lipids are targets for divalent cations due to electrostatic interactions with specific classes [ 16 , 17 ]. Divalent cations may cause increased membrane rigidity [ 18 ], aggregation [ 19 ], phase separation [ 20 ] and enhanced membrane permeability [ 21 ] in both model and isolated biological membranes.…”

Section: Introductionmentioning

confidence: 99%

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Lipid Structure Determines the Differential Impact of Single Metal Additions and Binary Mixtures of Manganese, Calcium and Magnesium on Membrane Fluidity and Liposome Size

Sule

Anikovskiy

Prenner

2023

IJMS

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Unilamellar vesicles of the biologically relevant lipids phosphatidic acid (PA) and phosphatidylserine (PS) with fully saturated (DM-) or partly unsaturated (PO-) acyl side chains were exposed to Ca, Mn and Mg in single metal additions; in equimolar mixtures or by sequential additions of one metal at a time. Laurdan generalized polarization measured the membrane fluidity, while dynamic light scattering reported liposome size changes complemented by zeta potential. All metals induced membrane rigidity and increased liposome sizes across all systems. Mn had the strongest effect overall, but Mg was comparable for DMPS. Lipid side chain architecture was important as GP values for binary mixtures were higher than expected from the sum of values for single additions added to POPS but smaller for DMPS. Sequential additions were predominantly different for Ca:Mg mixtures. Mn induced the strongest increase of liposome size in saturated lipids whereas Ca effects dominated unsaturated matrices. Binary additions induced larger sizes than the sum of single additions for POPS, but much lower changes in DMPA. The order of addition was relevant for PS systems. Thus, lipid structure determines metal effects, but their impact is modulated by other ions. Thus, metal effects may differ with the local lipid architecture and metal concentrations within cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Lipid Structure Determines the Differential Impact of Single Metal Additions and Binary Mixtures of Manganese, Calcium and Magnesium on Membrane Fluidity and Liposome Size

Sule

Anikovskiy

Prenner

2023

IJMS

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“…This is consistent with more fluid membranes that are more amenable to metal effects. The total GP increases at 50 °C (0.109) are the highest observed here, likely due to the negatively charged PS as the main species but the less prevalent PIs have been shown to be attractive targets for toxic metals like Cd 2+ and Pb 2+ [ 52 ] as well.…”

Section: Discussionmentioning

confidence: 97%

“…We previously estimated size changes that would be expected upon liposome fusion [ 52 ]. This is based on a published percentage of lipids in the outer leaflet [ 58 ], the molecular area of the lipids, and the size based on DLS.…”

Section: Discussionmentioning

confidence: 99%

Gadolinium Effects on Liposome Fluidity and Size Depend on the Headgroup and Side Chain Structure of Key Mammalian Brain Lipids

Farzi,

Issler,

Unruh

et al. 2023

Molecules

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The lanthanide metal gadolinium has been used in the healthcare industry as a paramagnetic contrast agent for years. Gadolinium deposition in brain tissue and kidneys has been reported following gadolinium-based contrast agent administration to patients undergoing MRI. This study demonstrates the detrimental effects of gadolinium exposure at the level of the cell membrane. Biophysical analysis using fluorescence spectroscopy and dynamic light scattering illustrates differential interactions of gadolinium ions with key classes of brain membrane lipids, including phosphatidylcholines and sphingomyelins, as well as brain polar extracts and biomimetic brain model membranes. Electrostatic attraction to negatively charged lipids like phosphatidylserine facilitates metal complexation but zwitterionic phosphatidylcholine and sphingomyelin interaction was also significant, leading to membrane rigidification and increases in liposome size. Effects were stronger for fully saturated over monounsaturated acyl chains. The metal targets key lipid classes of brain membranes and these biophysical changes could be very detrimental in biological membranes, suggesting that the potential negative impact of gadolinium contrast agents will require more scientific attention.

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Lipid headgroup and side chain architecture determine manganese-induced dose dependent membrane rigidification and liposome size increase

Sule

Prenner

2022

Eur Biophys J

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The degree and position of phosphorylation determine the impact of toxic and trace metals on phosphoinositide containing model membranes

Cited by 8 publications

References 105 publications

Lipid Structure Determines the Differential Impact of Single Metal Additions and Binary Mixtures of Manganese, Calcium and Magnesium on Membrane Fluidity and Liposome Size

Lipid Structure Determines the Differential Impact of Single Metal Additions and Binary Mixtures of Manganese, Calcium and Magnesium on Membrane Fluidity and Liposome Size

Gadolinium Effects on Liposome Fluidity and Size Depend on the Headgroup and Side Chain Structure of Key Mammalian Brain Lipids

Lipid headgroup and side chain architecture determine manganese-induced dose dependent membrane rigidification and liposome size increase

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