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Record W4408244740 · doi:10.1021/jacs.4c12543

Structure and pH Dependence of Membranolytic Mechanisms by Truncated Oxidized Phospholipids

2025· article· en· W4408244740 on OpenAlexafffund
Min Xie, Maik G. N. Derks, Eveline H. W. Koch, C. Bjorn van Boven, Minchakarn Janlad, Behnaz Bagheri, Zexi Xu, Daria Kovryzhenko, Cornelis A. van Walree, Ana Sobota, Markus Weingarth, Jirasak Wong-ekkabut, Mikko Karttunen, Eefjan Breukink, J. Antoinette Killian, Andreas F.‐P. Sonnen, Joseph H. Lorent

Bibliographic record

VenueJournal of the American Chemical Society · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicLipid Membrane Structure and Behavior
Canadian institutionsWestern University
FundersNatural Sciences and Engineering Research Council of CanadaAlliance de recherche numérique du CanadaChina Scholarship CouncilThailand Science Research and InnovationUniversiteit UtrechtTechnische Universiteit EindhovenFédération Wallonie-BruxellesCanada Research Chairs
KeywordsChemistryMembraneLipid bilayerBiophysicsBilayerMoleculeCell membraneCarboxylic acidBiochemistryOrganic chemistry

Abstract

fetched live from OpenAlex

Membrane lipid oxidation is a universal process that occurs in situations of oxidative stress and is encountered in numerous physiological and pathological situations. Oxidized truncated phospholipids make up a large part of the oxidation products and alter the membrane properties in a way that can lead to cell death. However, the underlying mechanisms are not well understood nor is it clear whether environmental factors, such as pH, can modulate these effects. Using model membranes, we investigate how individual lipid aldehydes and carboxylic acids with truncated acyl chains alter the membrane structure. Our data shows that lipid aldehydes and carboxylic acids have different permeabilization efficiencies towards molecules of varying charge and size and that ΔC9 truncated lipids are usually more efficient in permeabilizing membranes than ΔC5. In terms of physical mechanisms, the ΔC9 truncated lipid carboxylic acid induces permeabilization and membrane curvature in a pH-dependent fashion. This is explained by ionization-dependent exposure of the carboxyl group to the water-bilayer interface, which increases the intrinsic molecular curvature of the oxidized lipid. Conversely, ΔC9 truncated lipid aldehydes and nonionized carboxyls do not induce curved structures but are more efficient in increasing permeability toward larger molecules. We further show that truncated lipids can escape the bilayer and accumulate at interfaces, implying that they might act on neighboring cells. This study indicates that oxidized phospholipids with truncated acyl chains disrupt membrane structure, depending on their specific molecular structure and the pH of the environment, opening a possible route for the design of lipid nanoparticles with pH-dependent drug release.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.003
GPT teacher head0.232
Teacher spread0.229 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations9
Published2025
Admission routes2
Has abstractyes

Explore more

Same venueJournal of the American Chemical SocietySame topicLipid Membrane Structure and BehaviorFrench-language works237,207