{"doi":"10.1021/acs.jpcb.1c03559","title":"Physical Characterization of Triolein and Implications for Its Role in Lipid Droplet Biogenesis","abstract":"Lipid droplets (LDs) are neutral lipid-storing organelles surrounded by a phospholipid (PL) monolayer. At present, how LDs are formed in the endoplasmic reticulum (ER) bilayer is poorly understood. In this study, we present a revised all-atom (AA) triolein (TG) model, the main constituent of the LD core, and characterize its properties in a bilayer membrane to demonstrate the implications of its behavior in LD biogenesis. In bilayer simulations, TG resides at the surface, adopting PL-like conformations (denoted in this work as SURF-TG). Free energy sampling simulation results estimate the barrier for TG relocating from the bilayer surface to the bilayer center to be ∼2 kcal/mol in the absence of an oil lens. SURF-TG is able to modulate membrane properties by increasing PL ordering, decreasing bending modulus, and creating local negative curvature. The other neutral lipid, dioleoyl-glycerol (DAG), also reduces the membrane bending modulus and populates negative curvature regions. A phenomenological coarse-grained (CG) model is also developed to observe larger-scale SURF-TG-mediated membrane deformation. CG simulations confirm that TG nucleates between the bilayer leaflets at a critical concentration when SURF-TG is evenly distributed. However, when one monolayer contains more SURF-TG, the membrane bends toward the other leaflet, followed by TG nucleation if a concentration is higher than the critical threshold. The central conclusion of this study is that SURF-TG is a negative curvature inducer, as well as a membrane modulator. To this end, a model is proposed in which the accumulation of SURF-TG in the luminal leaflet bends the ER bilayer toward the cytosolic side, followed by TG nucleation.","journal":"The Journal of Physical Chemistry B","year":2021,"id":174330,"datarank":0.47670807455219194,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.0,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":246697,"name":"Gregory A. Voth","orcid":"0000-0002-3267-6748","position":1,"is_corresponding":false},{"id":287970,"name":"Siyoung Kim","orcid":"0000-0003-4670-9747","position":0,"is_corresponding":true}],"reference_count":120,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:46:54.772014Z","pmid":"34139844","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}