DOCSLIB.ORG

Molecular Dynamics Simulations of Lipid Membranes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Molecular Dynamics Simulations of Lipid Membranes MOLECULAR DYNAMICS SIMULATIONS OF LIPID MEMBRANES: THE EFFECTS OF PROBES, LIPID COMPOSITION AND PEPTIDES A Dissertation Presented to the Faculty of the Graduate School of Cornell University In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy by David Geoffrey Ackerman August 2015 © 2015 David Geoffrey Ackerman MOLECULAR DYNAMICS SIMULATIONS OF LIPID MEMBRANES: THE EFFECTS OF PROBES, LIPID COMPOSITION AND PEPTIDES David Geoffrey Ackerman, Ph.D. Cornell University 2015 The cell plasma membrane is comprised of hundreds of different lipid species as well as a variety of integral and peripheral proteins. The diversity of molecular constituents leads to the formation of functional lateral heterogeneities within the plane of the membrane, known as lipid rafts, which are distinct from the surrounding membrane. Given the complexity of the plasma membrane, and the importance of rafts in the life of a cell, simplified model mixtures capturing the characteristics of the plasma membrane have been essential for unraveling its underlying behavior. In this work, we use molecular dynamics simulations to study model membranes at resolutions not possible with experimental techniques. We first investigated a fundamental assumption in model membrane experiments: that extrinsic probes added to the membrane do not disrupt membrane behavior. We addressed this issue by simulating single component model membranes that contained commonly used fluorescent lipid analogs. We found that the probes are able to disorder the bilayer and reorient lipid headgroups due to the probes’ large, positively charged headgroups and long, interdigitating acyl chains. Importantly though, these effects die off within a couple of nanometers of the probe. This means that the probes do not disrupt large-scale membrane behavior and can effectively be used for experimental membrane studies. However, the short-ranged perturbations also indicate that probes may provide incorrect information if they report directly on their local, disrupted, environment. Next, we studied the behavior of more complex model membranes containing multiple lipid species. Experimentally, model membranes comprised of four lipid components can yield coexisting phases, mimicking raft and non-raft environments, ranging in size from nanometers to microns. Through simulations, we found that domain size and alignment are highly coupled and that they both change abruptly at certain lipid compositions. We also found that the phase interface between domains was only a couple of nanometers wide regardless of the properties of the two coexisting phases. Addition of transmembrane α-helical peptides of various lengths to the lipid-only mixtures significantly increased both domain size and alignment. These effects were largest for the shortest peptides and increased with peptide concentration. Thus cells may be able to control raft size and alignment, and in turn a variety of cellular processes, simply by altering lipid and protein concentrations. BIOGRAPHICAL SKETCH David Ackerman grew up on the south side of the tracks in Westfield, New Jersey. He persevered in a childhood without cable, often finding solace in public broadcasting and a variety of science and nature shows. Thanks to parents who never grew frustrated of his non-stop questions, and instead fed his curiosity with science articles and toys, David continued to find joy in science. Though set on pursuing a scientific education, in typical lazy David fashion, he did not enjoy putting in effort to actively seek out undergraduate institutions. Due to a suggestion by his father, David applied to and joined Northwestern University’s interdisciplinary Integrated Science Program in 2006. At Northwestern, David majored in integrated sciences, physics and math. Outside of classes, David performed theoretical research on extrasolar planets for Professor Fred Rasio. When it came time for graduate school, David decided to apply to institutions where he could use his broad scientific background to study problems at the boundaries between fields. David joined the Ph.D. program in Biophysics at Cornell University in 2010. He was interested in performing simulations, so logically he joined a predominantly experimental lab in a field in which he had no experience: Professor Gerald Feigenson’s membrane physical chemistry lab. As a member of Jerry’s lab, David has enjoyed performing research which links simulations to experiments. He hopes to continue using similar research methodologies in his next career, whenever and wherever that might be. iii To My Parents iv ACKNOWLEDGMENTS I would first like to thank my advisor Dr. Gerald Feigenson. Jerry is a constant source of knowledge and advice, and is invested in every project going on in the lab. His scientific integrity, passion and dedication are both inspirational and infectious. These traits, along with his willingness to let me pursue molecular dynamics even though neither he nor I had any experience with them, convinced me to join his lab. Throughout my 5 years at Cornell, he has been encouraging throughout my various projects spanning from simulations to experiments. It has been a real joy to work in his lab. Lab members past and present have also provided unique points of view which have benefited my work. These close friends and labmates include Dr. Fred Heberle, Dr. Lynda Goh, Dr. Robin Smith Petruzielo, (Fighting Mongeese Teammate) Dr. Jon Amazon, Dr. Tatyana Konyakhina, Milka Doktorova, Michael Weiner, Rebecca Simpson, Yi Wen, Dr. Kai Yang and the undergraduates Sanjula Wickramsinghe, Nimit Sohoni and Mary Kim. Additionally, I would like to thank my committee members Dr. John Brady and Dr. Warren Zipfel who provided guidance during my dissertation work and who took the time to attend my presentations and read my thesis. Importantly, my time in Ithaca has been made exponentially better by the friendships I have made here. Huimin Chen, Avtar Singh, Joshua Tokuda, Stella Li, Vinh Le, Jeahoo Kwon, Digbijay Mahat and Rupa Shah Mahat have put up with my annoying questions and stupid get rich quick schemes and have shown me how creativity, fun, a sense of adventure, and stupidity can thrive well into adulthood. Huimin has been an especially supportive, helpful, encouraging, adventurous, informative and important person during my years at Cornell. v Finally I would like to thank my family. My parents, Susan (aka Suebert) and Louis (aka Loubert), have been extremely caring and supportive throughout my life and always make sure I am prepared for what comes next, including making sure I always have my phone charger. My sisters Rachel and Sara have been successful in their very different careers and hobbies showing me what it takes to be successful when venturing out on my own. And of course my niece Esme, who always provides advice, whether it is in English, French or our own private language. Though research is often a somewhat independent endeavor, all these people have been essential to the successful completion of my dissertation. And for that, I am extremely grateful. vi TABLE OF CONTENTS TABLE OF CONTENTS .............................................................................................................. vii LIST OF FIGURES ........................................................................................................................ x LIST OF TABLES ........................................................................................................................ xii LIST OF ABBREVIATONS ....................................................................................................... xiii Chapter 1 Introduction........................................................................................................... 1 1.1 Overview ............................................................................................................................. 1 1.2 Lipid bilayer phases ............................................................................................................ 2 1.2 The cell plasma membrane ................................................................................................. 5 1.2.1 Plasma membrane composition ................................................................................. 5 1.2.2 Lateral membrane heterogeneity ................................................................................ 6 1.2.3 Lipid rafts ................................................................................................................... 8 1.3 Model membranes ............................................................................................................. 11 1.3.1 Model membrane components ................................................................................. 11 1.3.2 Ternary lipid mixtures .............................................................................................. 12 1.3.3 Type I and Type II ternary lipid mixtures ................................................................ 15 1.3.4 Quaternary lipid mixtures ........................................................................................ 16 1.3.5 Relevance to lipid rafts ............................................................................................ 18 1.4 Molecular dynamics (MD) simulations ............................................................................ 19 1.4.1 Basic MD methodology ........................................................................................... 19 1.4.2
Load more

Recommended publications
  • Download Product Insert (PDF)
    PRODUCT INFORMATION 1-Palmitoyl-2-oleoyl-sn-glycero-3-PC Item No. 15102 CAS Registry No.: 26853-31-6 Formal Name: 1-palmitoyl-2-oleoyl-sn-glycero-3- O phosphatidylcholine Synonyms: 1-Palmitoyl-2-oleoyl-sn-glycero-3- O O Phosphocholine, 1,2-POPC O MF: C42H82NO8P FW: 760.1 O N+ Purity: ≥98% O P O Supplied as: A crystalline solid O- Storage: -20°C Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures 1-Palmitoyl-2-oleoyl-sn-glycero-3-PC (1,2-POPC) is supplied as a crystalline solid. A stock solution may be made by dissolving the 1,2-POPC in the solvent of choice, which should be purged with an inert gas. 1,2-POPC is soluble in the organic solvent ethanol at a concentration of approximately 25 mg/ml. Description 1,2-POPC is a phospholipid containing 16:0 and 18:1 fatty acids at the sn-1 and sn-2 positions, respectively. It belongs to a class of phospholipids that are a major component of biological membranes.1,2 This compound can be used for liposome production in order to study the properties of lipid bilayers. References 1. Moreno, M.J., Estronca, L.M.B.B., and Vaz, W.L.C. Translocation of phospholipids and dithionite permeability in liquid-ordered and liquid-disordered membranes. Biophys. J. 91, 873-881 (2006). 2. Heberle, F.A. and Feigenson, G.W. Phase separation in lipid membranes. Cold Spring Harb. Perspect. Biol. 3(4), 1-13 (2011).
    [Show full text]
  • (4,5)-Bisphosphate Destabilizes the Membrane of Giant Unilamellar Vesicles
    5112 Biophysical Journal Volume 96 June 2009 5112–5121 Profilin Interaction with Phosphatidylinositol (4,5)-Bisphosphate Destabilizes the Membrane of Giant Unilamellar Vesicles Kannan Krishnan,† Oliver Holub,‡ Enrico Gratton,‡ Andrew H. A. Clayton,§ Stephen Cody,§ and Pierre D. J. Moens†* †Centre for Bioactive Discovery in Health and Ageing, School of Science and Technology, University of New England, Armidale, Australia; ‡Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California, Irvine, California; and §Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Victoria, Australia ABSTRACT Profilin, a small cytoskeletal protein, and phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] have been implicated in cellular events that alter the cell morphology, such as endocytosis, cell motility, and formation of the cleavage furrow during cytokinesis. Profilin has been shown to interact with PI(4,5)P2, but the role of this interaction is still poorly understood. Using giant unilamellar vesicles (GUVs) as a simple model of the cell membrane, we investigated the interaction between profilin and PI(4,5)P2. A number and brightness analysis demonstrated that in the absence of profilin, molar ratios of PI(4,5)P2 above 4% result in lipid demixing and cluster formations. Furthermore, adding profilin to GUVs made with 1% PI(4,5)P2 leads to the forma- tion of clusters of both profilin and PI(4,5)P2. However, due to the self-quenching of the dipyrrometheneboron difluoride-labeled PI(4,5)P2, we were unable to determine the size of these clusters. Finally, we show that the formation of these clusters results in the destabilization and deformation of the GUV membrane.
    [Show full text]
  • Influence of Cholesterol on Phospholipid Bilayers Phase Domains As Detected by Laurdan Fluorescence
    120 Biophysical Journal Volume 66 January 1994 120-132 Influence of Cholesterol on Phospholipid Bilayers Phase Domains as Detected by Laurdan Fluorescence Tiziana Parasassi,* Massimo Di Stefano,* Marianna Loiero,* Giampietro Ravagnan,* and Enrico Grattont *Istituto di Medicina Sperimentale, Consiglio Nazionale Ricerche, 00137 Rome, Italy, and tLaboratory for Fluorescence Dynamics, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA ABSTRACT Coexisting gel and liquid-crystalline phospholipid phase domains can be observed in synthetic phospholipid vesicles during the transition from one phase to the other and, in vesicles of mixed phospholipids, at intermediate temperatures between the transitions of the different phospholipids. The presence of cholesterol perturbs the dynamic properties of both phases to such an extent as to prevent the detection of coexisting phases. 6-Lauroyl-2-dimethylaminonaphthalene (Laurdan) fluorescence offers the unique advantage of well resolvable spectral parameters in the two phospholipid phases that can be used for the detection and quantitation of coexisting gel and liquid-crystalline domains. From Laurdan fluorescence excitation and emission spectra, the generalized polarization spectra and values were calculated. By the generalized polarization phos- pholipid phase domain coexistence can be detected, and each phase can be quantitated. In the same phospholipid vesicles where without cholesterol domain coexistence can be detected, above 15 mol % and, remarkably, at physiological cholesterol concentrations,
    [Show full text]
  • Cholesterol in Condensed and Fluid Phosphatidylcholine Monolayers Studied by Epifluorescence Microscopy
    Biophysical Journal Volume 72 June 1997 2569-2580 2569 Cholesterol in Condensed and Fluid Phosphatidylcholine Monolayers Studied by Epifluorescence Microscopy Lynn-Ann D. Worthman,* Kaushik Nag,* Philip J. Davis,* and Kevin M. W. Keough*# *Department of Biochemistry and #Discipline of Pediatrics, Memorial University of Newfoundland, St. John's, Newfoundland Al B 3X9, Canada ABSTRACT Epifluorescence microscopy was used to investigate the effect of cholesterol on monolayers of dipalmi- toylphosphatidylcholine (DPPC) and 1 -palmitoyl-2-oleoyl phosphatidylcholine (POPC) at 21 ± 20C using 1 mol% 1 -palmitoyl- 2-{1 2-[(7-nitro-2-1, 3-benzoxadizole-4-yl)amino]dodecanoyl}phosphatidylcholine (NBD-PC) as a fluorophore. Up to 30 mol% cholesterol in DPPC monolayers decreased the amounts of probe-excluded liquid-condensed (LC) phase at all surface pressures (ir), but did not effect the monolayers of POPC, which remained in the liquid-expanded (LE) phase at all 7r. At low (2-5 mN/m), 10 mol% or more cholesterol in DPPC induced a lateral phase separation into dark probe-excluded and light probe-rich regions. In POPC monolayers, phase separation was observed at low IT when .40 mol% or more cholesterol was present. The lateral phase separation observed with increased cholesterol concentrations in these lipid monolayers may be a result of the segregation of cholesterol-rich domains in ordered fluid phases that preferentially exclude the fluorescent probe. With increasing 7r, monolayers could be transformed from a heterogeneous dark and light appearance into a homogeneous fluorescent phase, in a manner that was dependent on ir and cholesterol content. The packing density of the acyl chains may be a determinant in the interaction of cholesterol with phosphatidylcholine (PC), because the transformations in monolayer surface texture were observed in phospholipid (PL)/sterol mixtures having similar molecular areas.
    [Show full text]
  • Chiral Supramolecular Architecture of Stable Transmembrane Pores
    www.nature.com/scientificreports OPEN Chiral supramolecular architecture of stable transmembrane pores formed by an α-helical antibiotic peptide in the presence of lyso- lipids Erik Strandberg1, David Bentz2, Parvesh Wadhwani1 & Anne S. Ulrich1,2* The amphipathic α-helical antimicrobial peptide MSI-103 (aka KIA21) can form stable transmembrane pores when the bilayer takes on a positive spontaneous curvature, e.g. by the addition of lyso-lipids. Solid-state 31P- and 15N-NMR demonstrated an enrichment of lyso-lipids in these toroidal wormholes. Anionic lyso-lipids provided additional stabilization by electrostatic interactions with the cationic peptides. The remaining lipid matrix did not afect the nature of the pore, as peptides maintained the same orientation independent of lipid charge, and a change in membrane thickness did not considerably afect their tilt angle. Under optimized conditions (i.e. in the presence of lyso-lipids and appropriate bilayer thickness), stable and well-aligned pores could be obtained for solid-state 2H-NMR analysis. These data revealed for the frst time the complete 3D alignment of this representative amphiphilic peptide in fuid membranes, which is compatible with either monomeric helices as constituents, or left- handed supercoiled dimers as building blocks from which the overall toroidal wormhole is assembled. Membrane-active antimicrobial peptides (AMPs) can kill microorganisms by permeabilizing the cell mem- brane. They are attracting much attention as potential new antibiotics against the increasingly common multidrug-resistant bacterial strains1–4. While it is clear that these peptides can target a wide range of microorgan- isms, the molecular mechanisms of membrane permeabilization are not yet fully characterized.
    [Show full text]
  • Disruption of Membrane Cholesterol Organization Impairs the Concerted Activity of PIEZO1 Channel Clusters
    bioRxiv preprint doi: https://doi.org/10.1101/604488; this version posted April 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Disruption of membrane cholesterol organization impairs the concerted activity of PIEZO1 channel clusters P. Ridone1,*, E. Pandzic2,*, M. Vassalli3, C. D. Cox1,5, A. Macmillan2, P.A. Gottlieb4 and B. Martinac1,5 1The Victor Chang Cardiac Research Institute, Lowy Packer Building, Darlinghurst, NSW 2010, Australia, 2Biomedical Imaging Facility (BMIF), Mark Wainwright Analytical Centre, Lowy Cancer Research Centre, The University of New South Wales, NSW, 2052, Australia , 3Institute of Biophysics, National Research Council, Genova, Italy , 4Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY, 14214, USA , 5St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010, Australia *These authors have equally contributed to this work Corresponding author: Dr. Boris Martinac Victor Chang Cardiac Research Institute Lowy Packer Building Darlinghurst, NSW 2010, Australia E-mail [email protected] Key words: Mechanosensitive channel, Cholesterol, STORM, Patch-Clamp, Fluorescence Microscopy. SUMMARY: The essential mammalian mechanosensitive channel PIEZO1 organizes in the plasma membrane into nanometric clusters which depend on the integrity of cholesterol domains to rapidly detect applied force and especially inactivate syncronously, the most commonly altered feature of PIEZO1 in pathology. 1 bioRxiv preprint doi: https://doi.org/10.1101/604488; this version posted April 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved.
    [Show full text]
  • New Insights on the Fluorescent Emission Spectra of Prodan and Laurdan
    J Fluoresc (2015) 25:621–629 DOI 10.1007/s10895-015-1545-x ORIGINAL PAPER New Insights on the Fluorescent Emission Spectra of Prodan and Laurdan Cíntia C. Vequi-Suplicy & Kaline Coutinho & M. Teresa Lamy Received: 12 December 2014 /Accepted: 23 February 2015 /Published online: 10 March 2015 # Springer Science+Business Media New York 2015 Abstract Prodan and Laurdan are fluorescent probes largely Introduction used in biological systems. They were synthetized to be sen- sitive to the environment polarity, and their fluorescent emis- The fluorescent probes Prodan (2-dimethylamino-6- sion spectrum shifts around 120 nm, from cyclohexane to propionylnaphthalene) and Laurdan (2-dimethylamino-6- water. Although accepted that their emission spectrum is com- dodecanoylnaphthalene) have been widely used in biological posed by two emission bands, the origin of these two bands is relevant systems [1–7]. They were synthetized [1]tobesen- still a matter of discussion. Here we analyze the fluorescent sitive to the environment polarity, so their emission spectra spectra of Prodan and Laurdan in solvents of different polar- shifts about 120 nm from cyclohexane to water [1, 8, 9]. ities, both by decomposing the spectrum into two Gaussian Moreover, when inserted into membranes, their emission bands and by computing the Decay Associated Spectra spectra is extremely dependent on the lipid bilayer phase (DAS), the latter with time resolved fluorescence. Our data (gel or fluid), the maximum of the spectrum shifting around show that the intensity of the lower energy emission band of 50 nm from one phase to the other [4, 6, 10]. Prodan and Laurdan (attributed, in the literature, to the decay Although Prodan and Laurdan have been extensively used, of a solvent relaxed state) is higher in cyclohexane than in their structure and electronic distribution, in different solvents, water, showing a decrease as the polarity of the medium in- are still a matter of discussion [11–13].
    [Show full text]
  • Biomimetic Curvature and Tension-Driven Membrane
    1 Biomimetic curvature and tension-driven membrane 2 fusion induced by silica nanoparticles 3 4 Marcos Arribas Perez1 and Paul A. Beales1,2,* 5 6 1 Astbury Centre for Structural Molecular Biology and School of Chemistry, University of Leeds, 7 Leeds, LS2 9JT, UK. 8 2 Bragg Centre for Materials Research, University of Leeds, Leeds, LS2 9JT, UK. 9 10 * Correspondence: [email protected] 11 12 1 13 Abstract 14 Membrane fusion is a key process to develop new technologies in synthetic biology, where 15 artificial cells function as biomimetic chemical microreactors. Fusion events in living cells are 16 intricate phenomena that require the coordinate action of multicomponent protein complexes. 17 However, simpler synthetic tools to control membrane fusion in artificial cells are highly desirable. 18 Native membrane fusion machinery mediates fusion driving a delicate balance of membrane 19 curvature and tension between two closely apposed membranes. Here we show that silica 20 nanoparticles (SiO2 NPs) at a size close to the cross-over between tension-driven and curvature- 21 driven interaction regimes initiate efficient fusion of biomimetic model membranes. Fusion 22 efficiency and mechanisms are studied by Förster Resonance Energy Transfer (FRET) and 23 confocal fluorescence microscopy. SiO2 NPs induce a slight increase in lipid packing likely to 24 increase the lateral tension of the membrane. We observe a connection between membrane 25 tension and fusion efficiency. Finally, real-time confocal fluorescence microscopy reveals three 26 distinct mechanistic pathways for membrane fusion. SiO2 NPs show significant potential for 27 inclusion in the synthetic biology toolkit for membrane remodelling and fusion in artificial cells.
    [Show full text]
  • Effects of Antidepressants on the Conformation of Phospholipid Headgroups Studied by Solid-State NMR
    MAGNETIC RESONANCE IN CHEMISTRY Magn. Reson. Chem. 2004; 42: 105–114 Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mrc.1327 Effects of antidepressants on the conformation of phospholipid headgroups studied by solid-state NMR Jose S. Santos,1† Dong-Kuk Lee1,2 and Ayyalusamy Ramamoorthy1,2,3∗ 1 Biophysics Research Division, University of Michigan, Ann Arbor, Michigan 48109-1055, USA 2 Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055, USA 3 Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Michigan 48109-1055, USA Received 10 June 2003; Revised 25 August 2003; Accepted 1 September 2003 The effect of tricyclic antidepressants (TCA) on phospholipid bilayer structure and dynamics was studied to provide insight into the mechanism of TCA-induced intracellular accumulation of lipids (known as lipidosis). Specifically we asked if the lipid–TCA interaction was TCA or lipid specific and if such physical interactions could contribute to lipidosis. These interactions were probed in multilamellar vesicles and mechanically oriented bilayers of mixed phosphatidylcholine–phosphatidylglycerol (PC–PG) phospholipids using 31Pand14N solid-state NMR techniques. Changes in bilayer architecture in the presence of TCAs were observed to be dependent on the TCA’s effective charge and steric constraints. The results further show that desipramine and imipramine evoke distinguishable changes on the membrane surface, particularly on the headgroup order, conformation and dynamics of phospholipids. Desipramine increases the disorder of the choline site at the phosphatidylcholine headgroup while leaving the conformation and dynamics of the phosphate region largely unchanged. Incorporation of imipramine changes both lipid headgroup conformation and dynamics.
    [Show full text]
  • Diethylstilbestrol Modifies the Structure of Model Membranes And
    biomolecules Article DiethylstilbestrolArticle Modifies the Structure of Model Membranes Diethylstilbestrol Modifies the Structure of Model Membranes andand Is Is Localized Localized Close Close to the First Carbons of the Fatty Acyl Chains AlessioAlessio Ausili, Inés Inés Rodríguez-González, Rodríguez-González, Alejandro Torrecillas, JosJoséé A.A. TeruelTeruel andand JuanJuan C.C. GGómez-Fernándezómez-Fernández ** Departamento de Bioquímica y Biología Molecular “A”, Facultad de Veterinaria, Regional Campus of Departamento de Bioquímica y Biología Molecular “A”, Facultad de Veterinaria, Regional Campus of International Excellence “Campus Mare Nostrum”, Universidad de Murcia, Apartado de Correos 4021, International Excellence “Campus Mare Nostrum”, Universidad de Murcia, Apartado de Correos 4021, E-30080-Murcia, Spain; [email protected] (A.A.); [email protected] (I.R.-G.); [email protected] (A.T.); E-30080 Murcia, Spain; [email protected] (A.A.); [email protected] (I.R.-G.); [email protected] (A.T.); [email protected] (J.A.T.) [email protected] (J.A.T.) ** Correspondence: [email protected]; Tel.: +34 +34-868-884-766;-868-884-766; Fax: +34968364147 +34-968-364-147 Abstract:Abstract: TheThe synthetic synthetic estrogen estrogen diethylstilbestrol diethylstilbestrol (DES) (DES) is is used used to to treat treat metastatic metastatic carcinomas carcinomas and and prostateprostate cancer. cancer. We We studied studied its its interaction interaction with with membranes membranes and and its its localization to to understand its its mechanismmechanism of of action action and and side-effects. side-effects. We We used used differential differential scanning scanning calorimetry calorimetry (DSC) (DSC) showing showing that DESthat fluidized DES fluidized the membrane the membrane and has and poor has solubility poor solubility in DMPC in DMPC (1,2-dimyristoyl- (1,2-dimyristoyl-sn-glycero-3-phos-sn-glycero-3- phocholine)phosphocholine) in the influid the state.
    [Show full text]
  • Phospholipid-Cellulose Interactions: Insight from Atomistic Computer Simulations for Understanding the Impact of Cellulose-Based Materials on Plasma Membranes
    bioRxiv preprint doi: https://doi.org/10.1101/425686; this version posted September 25, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Phospholipid-Cellulose Interactions: Insight from Atomistic Computer Simulations for Understanding the Impact of Cellulose-Based Materials on Plasma Membranes Andrey A. Gurtovenko,∗,† Evgenii I. Mukhamadiarov,‡ Andrei Yu. Kostritskii,‡ and Mikko Karttunen¶,§,† †Institute of Macromolecular Compounds, Russian Academy of Sciences, Bolshoi Prospect V.O. 31, St.Petersburg, 199004 Russia ‡Faculty of Physics, St.Petersburg State University, Ulyanovskaya str. 3, Petrodvorets, St.Petersburg, 198504 Russia ¶Department of Chemistry, the University of Western Ontario,1151 Richmond Street, London, Ontario, Canada N6A 3K7 §Department of Applied Mathematics, the University of Western Ontario, 1151 Richmond Street, London, Ontario, Canada N6A 5B7 E-mail: [email protected];Web:biosimu.org 1 bioRxiv preprint doi: https://doi.org/10.1101/425686; this version posted September 25, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract Cellulose is an important biocompatible and nontoxic polymer widely used in nu- merous biomedical applications. The impact of cellulose-based materials on cells and, more specifically, on plasma membranes that surround cells, however, remains poorly understood. To this end, here we performed atomic-scale molecular dynamics (MD) simulations of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) bilayers interacting with the surface of a cellulose crystal.
    [Show full text]
  • PCCP Accepted Manuscript
    PCCP Accepted Manuscript This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. www.rsc.org/pccp Page 1 of 16 Physical Chemistry Chemical Physics Effect of Lipid Head Group Interactions in Membrane Properties and Membrane-Induced Cationic β-Hairpin Folding† a,c b,c d Sai J Ganesan, , Hongcheng Xu, and Silvina Matysiak∗ Membrane interfaces (mIFs) are ubiquitous components of living cells and are host to many essential biological processes. One key characteristic of mIFs is the dielectric gradient and subsequently, electrostatic potential that arises from dipolar interactions in the head group region. In this work, we present a coarse-grained (CG) model for anionic and zwitterionic lipids that accounts for dipolar intricacies in the head group region.
    [Show full text]