{"entity": "researcher", "timestamp": "2026-10-10T11:44:20.556Z", "family": "Marquardt", "given": "Drew", "initials": "D", "orcid": "0000-0001-6848-2497", "affiliations": ["Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/114cdc1c929d46308422b3b587f8e1d6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/114cdc1c929d46308422b3b587f8e1d6"}}, "publications": [{"entity": "publication", "iuid": "a369585d7b334ff2a61235dee75bca06", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a369585d7b334ff2a61235dee75bca06.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a369585d7b334ff2a61235dee75bca06"}}, "title": "Probing the Link between Pancratistatin and Mitochondrial Apoptosis through Changes in the Membrane Dynamics on the Nanoscale.", "authors": [{"family": "Castillo", "given": "Stuart R", "initials": "SR"}, {"family": "Rickeard", "given": "Brett W", "initials": "BW"}, {"family": "DiPasquale", "given": "Mitchell", "initials": "M"}, {"family": "Nguyen", "given": "Michael H L", "initials": "MHL"}, {"family": "Lewis-Laurent", "given": "Aislyn", "initials": "A"}, {"family": "Doktorova", "given": "Milka", "initials": "M"}, {"family": "Kav", "given": "Batuhan", "initials": "B", "orcid": "0000-0003-4990-373X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f092a8f23a5544aabba740be69a05099.json"}}, {"family": "Miettinen", "given": "Markus S", "initials": "MS", "orcid": "0000-0002-3999-4722", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2d402ef290145c89c840c1f87a81b17.json"}}, {"family": "Nagao", "given": "Michihiro", "initials": "M", "orcid": "0000-0003-3617-251X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/164a39e5ea05484ca0f7b89d4d6e6b4b.json"}}, {"family": "Kelley", "given": "Elizabeth G", "initials": "EG", "orcid": "0000-0002-6128-8517", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c3bd8f6f01b941a49f4cecc77224ffeb.json"}}, {"family": "Marquardt", "given": "Drew", "initials": "D", "orcid": "0000-0001-6848-2497", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/114cdc1c929d46308422b3b587f8e1d6.json"}}], "type": "journal article", "published": "2022-06-06", "journal": {"title": "Mol. Pharm.", "issn": "1543-8392", "issn-l": "1543-8384", "volume": "19", "issue": "6", "pages": "1839-1852"}, "abstract": "Pancratistatin (PST) is a natural antiviral alkaloid that has demonstrated specificity toward cancerous cells and explicitly targets the mitochondria. PST initiates apoptosis while leaving healthy, noncancerous cells unscathed. However, the manner by which PST induces apoptosis remains elusive and impedes the advancement of PST as a natural anticancer therapeutic agent. Herein, we use neutron spin-echo (NSE) spectroscopy, molecular dynamics (MD) simulations, and supporting small angle scattering techniques to study PST's effect on membrane dynamics using biologically representative model membranes. Our data suggests that PST stiffens the inner mitochondrial membrane (IMM) by being preferentially associated with cardiolipin, which would lead to the relocation and release of cytochrome c. Second, PST has an ordering effect on the lipids and disrupts their distribution within the IMM, which would interfere with the maintenance and functionality of the active forms of proteins in the electron transport chain. These previously unreported findings implicate PST's effect on mitochondrial apoptosis.", "doi": "10.1021/acs.molpharmaceut.1c00926", "pmid": "35559658", "labels": {"Milka Doktorova": null, "DDLS Fellow": null}, "xrefs": [], "notes": [], "created": "2024-11-27T12:19:21.904Z", "modified": "2024-11-29T12:15:45.480Z"}, {"entity": "publication", "iuid": "670dca7a2dcb4b41b15488745596e258", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/670dca7a2dcb4b41b15488745596e258.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/670dca7a2dcb4b41b15488745596e258"}}, "title": "Molecular Structure of Sphingomyelin in Fluid Phase Bilayers Determined by the Joint Analysis of Small-Angle Neutron and X-ray Scattering Data.", "authors": [{"family": "Doktorova", "given": "Milka", "initials": "M"}, {"family": "Ku\u010derka", "given": "Norbert", "initials": "N"}, {"family": "Kinnun", "given": "Jacob J", "initials": "JJ"}, {"family": "Pan", "given": "Jianjun", "initials": "J", "orcid": "0000-0002-7042-0022", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/628f9fc2c91e4fcfac681556cc374bce.json"}}, {"family": "Marquardt", "given": "Drew", "initials": "D", "orcid": "0000-0001-6848-2497", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/114cdc1c929d46308422b3b587f8e1d6.json"}}, {"family": "Scott", "given": "Haden L", "initials": "HL"}, {"family": "Venable", "given": "Richard M", "initials": "RM"}, {"family": "Pastor", "given": "Richard W", "initials": "RW", "orcid": "0000-0002-2454-5131", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f560f99fbea446f5a41521ef83ff9ddd.json"}}, {"family": "Wassall", "given": "Stephen R", "initials": "SR"}, {"family": "Katsaras", "given": "John", "initials": "J"}, {"family": "Heberle", "given": "Frederick A", "initials": "FA", "orcid": "0000-0002-0424-3240", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2557f5621a0b4c87b5f4702fbc7b6bdb.json"}}], "type": "journal article", "published": "2020-06-25", "journal": {"title": "J Phys Chem B", "issn": "1520-5207", "issn-l": "1520-5207", "volume": "124", "issue": "25", "pages": "5186-5200"}, "abstract": "We have determined the fluid bilayer structure of palmitoyl sphingomyelin (PSM) and stearoyl sphingomyelin (SSM) by simultaneously analyzing small-angle neutron and X-ray scattering data. Using a newly developed scattering density profile (SDP) model for sphingomyelin lipids, we report structural parameters including the area per lipid, total bilayer thickness, and hydrocarbon thickness, in addition to lipid volumes determined by densitometry. Unconstrained all-atom simulations of PSM bilayers at 55 \u00b0C using the C36 CHARMM force field produced a lipid area of 56 \u00c52, a value that is 10% lower than the one determined experimentally by SDP analysis (61.9 \u00c52). Furthermore, scattering form factors calculated from the unconstrained simulations were in poor agreement with experimental form factors, even though segmental order parameter (SCD) profiles calculated from the simulations were in relatively good agreement with SCD profiles obtained from NMR experiments. Conversely, constrained area simulations at 61.9 \u00c52 resulted in good agreement between the simulation and experimental scattering form factors, but not with SCD profiles from NMR. We discuss possible reasons for the discrepancies between these two types of data that are frequently used as validation metrics for molecular dynamics force fields.", "doi": "10.1021/acs.jpcb.0c03389", "pmid": "32468822", "labels": {"Milka Doktorova": null, "DDLS Fellow": null}, "xrefs": [{"db": "mid", "key": "NIHMS1621132"}, {"db": "pmc", "key": "PMC7458099"}], "notes": [], "created": "2024-11-27T12:16:11.940Z", "modified": "2024-11-29T12:16:19.122Z"}, {"entity": "publication", "iuid": "7cc9ceb62973482195d1ed302e5c3ff6", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7cc9ceb62973482195d1ed302e5c3ff6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7cc9ceb62973482195d1ed302e5c3ff6"}}, "title": "Peptide-Induced Lipid Flip-Flop in Asymmetric Liposomes Measured by Small Angle Neutron Scattering.", "authors": [{"family": "Nguyen", "given": "Michael H L", "initials": "MHL"}, {"family": "DiPasquale", "given": "Mitchell", "initials": "M"}, {"family": "Rickeard", "given": "Brett W", "initials": "BW"}, {"family": "Doktorova", "given": "Milka", "initials": "M"}, {"family": "Heberle", "given": "Frederick A", "initials": "FA", "orcid": "0000-0002-0424-3240", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2557f5621a0b4c87b5f4702fbc7b6bdb.json"}}, {"family": "Scott", "given": "Haden L", "initials": "HL"}, {"family": "Barrera", "given": "Francisco N", "initials": "FN"}, {"family": "Taylor", "given": "Graham", "initials": "G"}, {"family": "Collier", "given": "Charles P", "initials": "CP", "orcid": "0000-0002-8198-793X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c9ebfa8b6f4d4fafaccc956166f0a187.json"}}, {"family": "Stanley", "given": "Christopher B", "initials": "CB", "orcid": "0000-0002-4226-7710", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d6a186b9b434487907f1035cb1c8edf.json"}}, {"family": "Katsaras", "given": "John", "initials": "J"}, {"family": "Marquardt", "given": "Drew", "initials": "D", "orcid": "0000-0001-6848-2497", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/114cdc1c929d46308422b3b587f8e1d6.json"}}], "type": "journal article", "published": "2019-09-10", "journal": {"title": "Langmuir", "issn": "1520-5827", "issn-l": "0743-7463", "volume": "35", "issue": "36", "pages": "11735-11744"}, "abstract": "Despite the prevalence of lipid transbilayer asymmetry in natural plasma membranes, most biomimetic model membranes studied are symmetric. Recent advances have helped to overcome the difficulties in preparing asymmetric liposomes in vitro, allowing for the examination of a larger set of relevant biophysical questions. Here, we investigate the stability of asymmetric bilayers by measuring lipid flip-flop with time-resolved small-angle neutron scattering (SANS). Asymmetric large unilamellar vesicles with inner bilayer leaflets containing predominantly 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and outer leaflets composed mainly of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) displayed slow spontaneous flip-flop at 37 \u25e6C (half-time, t1/2 = 140 h). However, inclusion of peptides, namely, gramicidin, alamethicin, melittin, or pHLIP (i.e., pH-low insertion peptide), accelerated lipid flip-flop. For three of these peptides (i.e., pHLIP, alamethicin, and melittin), each of which was added externally to preformed asymmetric vesicles, we observed a completely scrambled bilayer in less than 2 h. Gramicidin, on the other hand, was preincorporated during the formation of the asymmetric liposomes and showed a time resolvable 8-fold increase in the rate of lipid asymmetry loss. These results point to a membrane surface-related (e.g., adsorption/insertion) event as the primary driver of lipid scrambling in the asymmetric model membranes of this study. We discuss the implications of membrane peptide binding, conformation, and insertion on lipid asymmetry.", "doi": "10.1021/acs.langmuir.9b01625", "pmid": "31408345", "labels": {"Milka Doktorova": null, "DDLS Fellow": null}, "xrefs": [{"db": "mid", "key": "NIHMS1612790"}, {"db": "pmc", "key": "PMC7393738"}], "notes": [], "created": "2024-11-27T12:18:10.589Z", "modified": "2024-11-29T12:16:50.099Z"}, {"entity": "publication", "iuid": "2f07c62cc1f443868e9a6013aec27ba4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2f07c62cc1f443868e9a6013aec27ba4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2f07c62cc1f443868e9a6013aec27ba4"}}, "title": "Preparation of asymmetric phospholipid vesicles for use as cell membrane models.", "authors": [{"family": "Doktorova", "given": "Milka", "initials": "M", "orcid": "0000-0003-4366-2242", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/791384c319f04584bac8ffb21df7271f.json"}}, {"family": "Heberle", "given": "Frederick A", "initials": "FA", "orcid": "0000-0002-0424-3240", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2557f5621a0b4c87b5f4702fbc7b6bdb.json"}}, {"family": "Eicher", "given": "Barbara", "initials": "B"}, {"family": "Standaert", "given": "Robert F", "initials": "RF"}, {"family": "Katsaras", "given": "John", "initials": "J", "orcid": "0000-0002-0424-3240", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2557f5621a0b4c87b5f4702fbc7b6bdb.json"}}, {"family": "London", "given": "Erwin", "initials": "E", "orcid": "0000-0002-1295-0113", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/65792417577b43f48d05e1e00ee94415.json"}}, {"family": "Pabst", "given": "Georg", "initials": "G", "orcid": "0000-0003-1967-1536", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec4ae71525c9411ea39715388b46afee.json"}}, {"family": "Marquardt", "given": "Drew", "initials": "D", "orcid": "0000-0001-6848-2497", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/114cdc1c929d46308422b3b587f8e1d6.json"}}], "type": "journal article", "published": "2018-09-00", "journal": {"title": "Nat Protoc", "issn": "1750-2799", "issn-l": null, "volume": "13", "issue": "9", "pages": "2086-2101"}, "abstract": "Freely suspended liposomes are widely used as model membranes for studying lipid-lipid and protein-lipid interactions. Liposomes prepared by conventional methods have chemically identical bilayer leaflets. By contrast, living cells actively maintain different lipid compositions in the two leaflets of the plasma membrane, resulting in asymmetric membrane properties that are critical for normal cell function. Here, we present a protocol for the preparation of unilamellar asymmetric phospholipid vesicles that better mimic biological membranes. Asymmetry is generated by methyl-\u03b2-cyclodextrin-catalyzed exchange of the outer leaflet lipids between vesicle pools of differing lipid composition. Lipid destined for the outer leaflet of the asymmetric vesicles is provided by heavy-donor multilamellar vesicles containing a dense sucrose core. Donor lipid is exchanged into extruded unilamellar acceptor vesicles that lack the sucrose core, facilitating the post-exchange separation of the donor and acceptor pools by centrifugation because of differences in vesicle size and density. We present two complementary assays allowing quantification of each leaflet's lipid composition: the overall lipid composition is determined by gas chromatography-mass spectrometry, whereas the lipid distribution between the two leaflets is determined by NMR, using the lanthanide shift reagent Pr3+. The preparation protocol and the chromatographic assay can be applied to any type of phospholipid bilayer, whereas the NMR assay is specific to lipids with choline-containing headgroups, such as phosphatidylcholine and sphingomyelin. In ~12 h, the protocol can produce a large yield of asymmetric vesicles (up to 20 mg) suitable for a wide range of biophysical studies.", "doi": "10.1038/s41596-018-0033-6", "pmid": "30190552", "labels": {"Milka Doktorova": null, "DDLS Fellow": null}, "xrefs": [{"db": "mid", "key": "EMS82425"}, {"db": "pmc", "key": "PMC6459367"}, {"db": "pii", "key": "10.1038/s41596-018-0033-6"}], "notes": [], "created": "2024-11-27T12:17:12.634Z", "modified": "2024-11-29T10:50:07.950Z"}]}