Research Article Special Issues

Interdisciplinary approaches to the study of biological membranes

  • Received: 01 May 2020 Accepted: 22 June 2020 Published: 08 July 2020
  • The investigation of the structural features in biological membranes represents a central topic in many aspects of biological science. It involves the study of the collective behavior of a great number of interacting macromolecules, while the study of the structure-function relationship require the observation and calculation of a large number of key factors. The self-assembly processes involved in biomembranes represent the cornerstone of the biological systems functioning, due to the special role of the complex macromolecular assemblies containing lipids, proteins, carbohydrates, nucleic acids, and other active components. In this article, we describe the main techniques and approaches employed for the investigation of biological membranes, which are characterized by a wide range of the space-time domains. The future challenge in this research field must provide the integration of the different research models and approaches into a common background based on multi- and interdisciplinary method that combine the expertise coming from the different disciplines.

    Citation: Domenico Lombardo, Pietro Calandra, Maria Teresa Caccamo, Salvatore Magazù, Luigi Pasqua, Mikhail A. Kiselev. Interdisciplinary approaches to the study of biological membranes[J]. AIMS Biophysics, 2020, 7(4): 267-290. doi: 10.3934/biophy.2020020

    Related Papers:

  • The investigation of the structural features in biological membranes represents a central topic in many aspects of biological science. It involves the study of the collective behavior of a great number of interacting macromolecules, while the study of the structure-function relationship require the observation and calculation of a large number of key factors. The self-assembly processes involved in biomembranes represent the cornerstone of the biological systems functioning, due to the special role of the complex macromolecular assemblies containing lipids, proteins, carbohydrates, nucleic acids, and other active components. In this article, we describe the main techniques and approaches employed for the investigation of biological membranes, which are characterized by a wide range of the space-time domains. The future challenge in this research field must provide the integration of the different research models and approaches into a common background based on multi- and interdisciplinary method that combine the expertise coming from the different disciplines.


    加载中


    Conflict of interest



    The authors declare no conflict of interest.

    [1] Sackmann E (1995) Physical basis of self-organization and function of membranes: physics of vesicles. Handbook Biol Phys 1: 213-304.
    [2] Goni FM (2014) The basic structure and dynamics of cell membranes: an update of the Singer-Nicolson model. Biochim Biophys Acta 1838: 1467-1476.
    [3] Devaux PF (1991) Static and dynamic lipid asymmetry in cell membranes. Biochemistry 30: 1163-1173.
    [4] Tanford C (1973)  The Hydrophobic Effect: Formation of Micelles and Biological Membranes New York: John Wiley and Sons Inc..
    [5] Ishida T, Harashima H, Kiwada H, et al. (2002) Liposome clearance. Biosci Rep 22: 197-224.
    [6] Allen TM, Cullis PR (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 65: 36-48.
    [7] Bobo D, Robinson KJ, Islam J, et al. (2016) Nanoparticle-based medicines: a review of FDA-approved materials and clinical trials to date. Pharm Res 33: 2373-2387.
    [8] Lombardo D, Calandra P, Barreca D, et al. (2016) Soft interaction in liposome nanocarriers for therapeutic drug delivery. Nanomaterials 6: 125.
    [9] Ceh B, Lasic DD (1995) A rigorous theory of remote loading of drugs into liposomes. Langmuir 11: 3356-3368.
    [10] Katsaras J, Gutberlet T (2000)  Lipid Bilayers: Structure and Interactions Berlin: Springer-Verlag Berlin Heidelberg.
    [11] Moore TL, Rodriguez-Lorenzo L, Hirsch V, et al. (2015) Nanoparticle colloidal stability in cell culture media and impact on cellular interactions. Chem Soc Rev 44: 6287-6305.
    [12] Xing H, Hwang K, Lu Y (2016) Recent developments of liposomes as nanocarriers for theranostic applications. Theranostics 6: 1336-1352.
    [13] Lombardo D, Calandra P, Magazù S, et al. (2018) Soft nanoparticles charge expression within lipid membranes: the case of amino terminated dendrimers in bilayers vesicles. Colloid Surface B 170: 609-616.
    [14] Lombardo D, Calandra P, Caccamo MT, et al. (2019) Colloidal stability of liposomes. AIMS Mater Sci 6: 200.
    [15] Gennis RB (1998)  Biomembranes: Molecular Structure and Function New York: Springer-Verlag.
    [16] Singer SJ, Nicolson GL (1072) The fluid mosaic model of the structure of cell membranes. Science 175: 720-731.
    [17] Dowhan W, Bogdanov M (2011) Lipid–protein interactions as determinants of membrane protein structure and function. Biochem Soc Trans 39: 767-774.
    [18] Liu Z, Persson S, Zhang Y (2015) The connection of cytoskeletal network with plasma membrane and the cell wall. J Integr Plant Biol 57: 330-340.
    [19] Bezanilla M, Gladfelter AS, Kovar DR, et al. (2015) Cytoskeletal dynamics: a view from the membrane. J Cell Biol 209: 329-337.
    [20] Simons K, Toomre D (2000) Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 1: 31-39.
    [21] Simons K, Ehehalt R (2002) Cholesterol, lipid rafts, and disease. J Clin Invest 110: 597-603.
    [22] Jacobson K, Mouritsen OG, Anderson RGW (2007) Lipid rafts: at a crossroad between cell biology and physics. Nat Cell Biol 9: 7-14.
    [23] Lingwood D, Simons K (2010) Lipid rafts as a membrane-organizing principle. Science 327: 46-50.
    [24] Frisz JF, Lou K, Klitzing HA, et al. (2013) Direct chemical evidence for sphingolipid domains in the plasma membranes of fibroblasts. Proc Natl Acad Sci USA 110: E613-E622.
    [25] Lorent JH, Levental KR, Ganesan L, et al. (2020) Plasma membranes are asymmetric in lipid unsaturation, packing and protein shape. Nat Chem Biol 16: 644-652.
    [26] Risselada HJ (2019) Cholesterol: The plasma membrane's constituent that chooses sides. Biophys J 116: 2235-2236.
    [27] Liu SL, Sheng R, Jung JH, et al. (2017) Orthogonal lipid sensors identify transbilayer asymmetry of plasma membrane cholesterol. Nat Chem Biol 13: 268-274.
    [28] Sevcsik E, Schütz GJ (2016) With or without rafts? alternative views on cell membranes. Bioessays 38: 129-139.
    [29] Fantini J, Barrantes FJ (2018) How membrane lipids control the 3D structure and function of receptors. AIMS Biophys 5: 22-35.
    [30] Disalvo EA (2015)  Membrane Hydration the Role of Water in the Structure and Function of Biological Membranes Switzerland: Springer International Publishing.
    [31] Israelachvili J, Wennerström H (1996) Role of hydration and water structure in biological and colloidal interactions. Nature 379: 219-225.
    [32] Branca C, Magazù S, Migliardo F, et al. (2002) Destructuring effect of trehalose on the tetrahedral network of water: A raman and neutron diffraction comparison. Phys A 304: 314-318.
    [33] Maisano G, Majolino D, Migliardo P (1993) Sound velocity and hydration phenomena in aqueous polymeric solutions. Mol Phys 78: 421-435.
    [34] Franks F (1975)  Water, a Comprehensive Treatise New York: Springher.
    [35] Kumar R, Keyes T (2001) The relation between the structure of the first solvation shell and the ir spectra of aqueous solutions. J Biol Phys 38: 75-83.
    [36] Fenimore PW, Frauenfelder H, Magazù S, et al. (2013) Concepts and problems in protein dynamics. Chem Phys 424: 2-6.
    [37] Minutoli L, Altavilla D, Bitto A, et al. (2008) A biophysics approach to modulate the inflammatory response during endotoxic shock. Eur J Pharmacol 589: 272-280.
    [38] Disalvo EA, Lairion F, Martini F, et al. (2008) Structural and functional properties of hydration and confined water in membrane interfaces. Biochim Biophys Acta Biomembr 1778: 2655-2670.
    [39] Roy A, Dutta R, Kundu N, et al. (2016) A aomparative study of the influence of sugars sucrose, trehalose, and maltose on the hydration and diffusion of DMPC lipid bilayer at complete hydration: investigation of structural and spectroscopic aspect of lipid–sugar interaction. Langmuir 32: 5124-5134.
    [40] Cannuli A, Caccamo MT, Castorina G, et al. (2018) Laser techniques on acoustically levitated droplets. EPJ Web of Conferences 167: 5010.
    [41] Caccamo MT, Zammuto V, Gugliandolo C (2018) Thermal restraint of a bacterial exopolysaccharide of shallow vent origin. Int J Biol Macromol 114: 649-655.
    [42] Moiset G, López CA, Bartelds R, et al. (2014) Disaccharides impact the lateral organization of lipid membranes. J Am Chem Soc 136: 16167-16175.
    [43] Magazù S, Migliardo F, Benedetto A (2011) Elastic incoherent neutron scattering operating by varying instrumental energy resolution: principle, simulations, and experiments of the resolution elastic neutron scattering (rens). Rev Sci Instrum 82: 105115.
    [44] Migliardo F, Caccamo MT, Magazù S (2013) Elastic incoherent neutron scatterings wavevector and thermal analysis on glass-forming homologous disaccharides. J non-cryst solids 378: 144-151.
    [45] Israelachvili J, Wennerström H (1996) Role of hydration and water structure in biological and colloidal interactions. Nature 379: 219-225.
    [46] Kiselev MA, Lesieur P, Kisselev AM, et al. (2001) A sucrose solutions application to the study of model biological membranes. Nucl Instrum Meth A 470: 409-416.
    [47] Kiselev MA, Lesieur P, Kisselev AM, et al. (2001) Sucrose solutions as prospective medium to study the vesicle structure: SAXS and SANS study. J Alloys Comps 328: 71-76.
    [48] Bourgaux C, Couvreur P (2014) Interactions of anticancer drugs with biomembranes: what can we learn from model membranes? J Control Release 190: 127-138.
    [49] Helrich CS (2017) Studies of cholesterol structures in phospholipid bilayers. AIMS Biophysics 4: 415-437.
    [50] Contini C, Schneemilch M, Gaisford S, et al. (2018) Nanoparticle–membrane interactions. J Exp Nanosci 13: 62-81.
    [51] Nel AE, Madler L, Velegol D, et al. (2009) Understanding biophysicochemical interactions at the nano–bio interface. Nat Mater 8: 543-557.
    [52] Mashaghi A, Mashaghi S, Reviakine I, et al. (2014) Label-free characterization of biomembranes: from structure to dynamics. Chem Soc Rev 43: 887-900.
    [53] Grabielle-Madelmont C, Lesieur S, Ollivon M (2003) Characterization of loaded liposomes by size exclusion chromatography. J Bioch Bioph Meth 56: 189-217.
    [54] Ong S, Liu H, Pidgeon C (1996) Immobilized artificial membrane chromatography: measurements of membrane partition coefficient and predicting drug membrane permeability. J Chromatogr A 728: 113-128.
    [55] Barbato F (2006) The use of Immobilised artificial membrane (iam) chromatography for determination of lipophilicity. Curr Comp Aided Drug Design 2: 341-352.
    [56] Stępnik KE, Malinowska I (2013) The use of biopartitioning micellar chromatography and immobilized artificial membrane column for in silico and in vitro determination of blood-brain barrier penetration of phenols. J Chromatogr A 1286: 127-136.
    [57] Russo G, Grumetto L, Szucs R, et al. (2017) Determination of in vitro and in silico indexes for the modeling of blood-brain barrier partitioning of drugs via micellar and immobilized artificial membrane liquid chromatography. J Med Chem 60: 3739-3754.
    [58] Liang C, Lian H (2015) Recent advances in lipophilicity measurement by reversed-phase high-performance liquid chromatography. TrAC Trend Anal Chem 68: 28-36.
    [59] De Vrieze M, Lynen F, Che K, et al. (2013) Predicting drug penetration across the blood-brain barrier: comparison of micellar liquid chromatography and immobilized artificial membrane liquid chromatography. Anal Bioanal Chem 405: 6029-6041.
    [60] Fitter J, Gutberlet T, Katsaras J (2006)  Neutron Scattering in Biology Techniques and Applications Heidelberg: Springer.
    [61] Nagle JF, Tristram-Nagle S (2000) Structure of lipid bilayers. BBA-Rev Biomembr 1469: 159-195.
    [62] Kiselev MA, Lombardo D (2017) Structural characterization in mixed lipid membrane systems by neutron and x-ray scattering. BBA-Gen Subjects 1861: 3700-3717.
    [63] Lesieur P, Kiselev MA, Barsukov LI, et al. (2000) Temperature-induced micelle to vesicle transition: Kinetic effects in the DMPC/NaC system. J Appl Cryst 33: 623-627.
    [64] Di Cola E, Grillo I, Ristori S (2016) Small angle x-ray and neutron scattering: powerful tools for studying the structure of drug-loaded liposomes. Pharmaceutics 8: 10.
    [65] Eicher B, Heberle FA, Marquardt D, et al. (2017) Joint small-angle x-ray and neutron scattering data analysis of asymmetric lipid vesicles. J Appl Cryst 50: 419-429.
    [66] Kiselev MA, Janich M, Hildebrand A, et al. (2013) Structural transition in aqueous lipid/bile salt [DPPC/NaDC] supramolecular aggregates: sans and dls study. Chem Phys 424: 93-99.
    [67] Kiselev MA, Lombardo D, Lesieur P, et al. (2008) Membrane self assembly in mixed DMPC/NaC systems by sans. Chem Phys 345: 173-180.
    [68] Domenici F, Dell'Unto F, Triggiani D, et al. (2015) Vertical ordering sensitivity of solid supported dppc membrane to alamethicin and the related loss of cell viability. BBA Gen Subjects 1850: 759-768.
    [69] Büldt G, Gally HU, Seelig A, et al. (1978) Neutron diffraction studies on selectively deuterated phospholipid bilayers. Nature 271: 182-184.
    [70] Kiselev MA, Zemlyanaya EV, Ryabova NY, et al. (2014) Influence of ceramide on the internal structure and hydration of the phospholipid bilayer studied by neutron and x-ray scattering. Appl Phys A 116: 319-325.
    [71] Umegawa Y, Matsumori N, Murata M (2018) Chapter two-Recent solid-state NMR studies of hydrated lipid membranes. Annu Rep NMR Spectrosc 94: 41-72.
    [72] Perrin JC, Lyonnard S, Guillermo A, et al. (2006) Water dynamics in ionomer membranes by field-cycling NMR relaxometry. J Phys Chem B 110: 5439-5444.
    [73] Kimmich R (2019)  Field-Cycling NMR Relaxometry: Instrumentation, Model Theories and Applications London: the Royal Society of Chemistry.
    [74] Mallikarjunaiah KJ, Kinnun JJ, Petrache HI, et al. (2019) Flexible lipid nanomaterials studied by NMR spectroscopy. Phys Chem Chem Phys 21: 18422-18457.
    [75] Yang J, Maragliano C, Schmidt AJ (2013) Thermal property microscopy with frequency domain thermoreflectance. Rev Sci Instrum 84: 104904.
    [76] Todosijevic SZ, Soskic ZN, Galovic SP (2016) A combination of frequency photoacoustic and photoacoustic spectroscopy techniques for measurement of optical and thermal properties of macromolecular nanostructures. Opt Quant Electron 48: 300.
    [77] Rochowski P, Niedziałkowski P, Pogorzelski SJ (2020) The benefits of photoacoustics for the monitoring of drug stability and penetration through tissue-mimicking membranes. Int J Pharm 580: 119233.
    [78] Nieh MP, Heberle FA, Katsaras J (2019)  Characterization of Biological Membranes Structure and Dynamics De Gruyter Edition.
    [79] Pignatello R, Musumeci T, Basile L (2011) Biomembrane models and drug-biomembrane interaction studies: involvement in drug design and development. J Pharm Bioallied Sci 3: 4-14.
    [80] Pignatello R (2013)  Drug-Biomembrane Interaction Studies, the Application of Calorimetric Techniques Amsterdam: Elsevier.
    [81] Abraham T, Lewis RNAH, Hodges RS, et al. (2005) Isothermal titration calorimetry studies of the binding of a rationally designed analogue of the antimicrobial peptide gramicidin s to phospholipid bilayer membranes. Biochemistry 44: 2103-2112.
    [82] Helvig S, Azmi IDM, Moghimi SM, et al. (2015) Recent advances in cryo-TEM imaging of soft lipid nanoparticles. AIMS Biophysics 2: 116-130.
    [83] Almgren M, Edwards K, Karlsson G (2000) Cryo transmission electron microscopy of liposomes and related structures. Colloids Surf A 174: 3-21.
    [84] van Zanten TS, Cambi A, Garcia-Parajo MF (2010) A nanometer scale optical view on the compartmentalization of cell membranes. Biochim Biophys Acta 1798: 777-787.
    [85] Elson EL (2011) Fluorescence correlation spectroscopy: past, present, future. Biophys J 101: 2855-2870.
    [86] Peter SC, Dhanjal JK, Malik V, et al. (2019) Quantitative structure-activity relationship (QSAR): modeling approaches to biological applications. Encyclopedia Bioinf Comput Biol 2: 661-676.
    [87] Berthod A, García-Alvarez-Coque MC (2000)  Micellar Liquid Chromatography New York: Marcel Dekker.
    [88] Bermúdez-Saldaña JM, Escuder-Gilabert L, Medina-Hernández MJ, et al. (2007) Biopartitioning micellar chromatography: an alternative high-throughput method for assessing the ecotoxicity of anilines and phenols. J Chromatogr B 852: 353.
    [89] Abraham MH, Platts JA, Begley M, et al. (2000)  The Blood–Brain Barrier and Drug Delivery to the CNS New York: Marcel Dekker.
    [90] Hansen JP, Mc Donald IR (3013)  Theory of Simple Liquids New York: Academic Press.
    [91] Hunter RJ (1986)  Foundations of Colloid Science Oxford: Oxford University Press.
    [92] Likos CN (2001) Effective interactions in soft condensed matter physics. Phys Rep 348: 267-439.
    [93] Belloni L (1991) Interacting monodisperse and polydisperse spheres. Neutron X-Ray and Light Scattering New York: Elsevier Science Publishers B.V..
    [94] Hamley IW (2003) Nanotechnology with soft materials. Angew Chem Int Ed Engl 42: 1692-1712.
    [95] Lombardo D, Munaò G, Calandra P, et al. (2019) Evidence of pre-micellar aggregates in aqueous solution of amphiphilic pdms-peo block copolymer. Phys Chem Chem Phys 21: 11983-11991.
    [96] Liveri VT, Lombardo D, Pochylski M, et al. (2018) Molecular association of small amphiphiles: origin of ionic liquid properties in dibutyl phosphate/propylamine binary mixtures. J Mol Liq 263: 274-281.
    [97] Lombardo D, Micali N, Villari V, et al. (2004) Large structures in diblock copolymer micellar solution. Phys Rev E 70: 021402.
    [98] Clarke J, Pappu RV, Berezovsky JN, et al. (2017)  Folding and binding proteins: bridging theory and experiment Amsterdam: Elsevier.
    [99] Lombardo D (2014) Modeling dendrimers charge interaction in solution: relevance in biosystems. Biochem Res Int 2014: 837651.
    [100] Porcar L, Hong K, Butler PD, et al. (2010) Intramolecular structural change of pamam dendrimers in aqueous solutions revealed by small-angle neutron scattering. J Chem Phys B 114: 1751-1756.
    [101] Li Q (2018)  Functional Organic and Hybrid Nanostructured Materials: Fabrication, Properties, and Applications Weinheim: Wiley-VCH Verlag GmbH and Co. KGaA.
    [102] Bonaccorsi L, Calandra P, Kiselev MA, et al. (2013) Self-assembly in poly(dimethylsiloxane)-poly(ethylene oxide) block copolymer template directed synthesis of linde type A zeolite. Langmuir 29: 7079-7086.
    [103] Bonaccorsi L, Calandra P, Amenitsch H, et al. (2013) Growth of fractal aggregates during template directed sapo-34 zeolite formation. Micropor Mesopor Mat 167: 3-9.
    [104] Nel AE, Madler L, Velegol D, et al. (2009) Understanding biophysicochemical interactions at the nano–bio interface. Nat Mater 8: 543-557.
    [105] Lombardo D, Calandra P, Bellocco E, et al. (2016) Effect of anionic and cationic polyamidoamine (PAMAM) dendrimers on a model lipid membrane. Biochim Biophys Acta Biomembr 1858: 2769-2777.
    [106] Saiz l, Klein ML (2002) Computer simulation studies of model biological membranes. Acc Chem Res 35: 482-489.
    [107] Deserno M, Kremer K, Paulsen H, et al. (2013) Computational studies of biomembrane systems: theoretical considerations, simulation models, and applications. From Single Molecules to Nanoscopically Structured Materials. Advances in Polymer Science Cham: Springer.
    [108] Nguyen TH, Moore CC, Moore PB, et al. (2018) Molecular dynamics study of homo-oligomeric ion channels: structures of the surrounding lipids and dynamics of water movement. AIMS Biophysics 5: 50-76.
    [109] Koufos E, Muralidharan B, Dutt M (2014) Computational design of multi-component bio-Inspired bilayer membranes. AIMS Mater Sci 1: 103-120.
    [110] Lyubartseva AP, Rabinovich AL (2015) Force field development for lipid membrane simulations. Biochim Biophys Acta Biomembr 1858: 2483-2497.
    [111] Pluhackova K, Böckmann RA (2015) Biomembranes in atomistic and coarse-grained simulations. J Phys Condens Matter 27: 323103.
    [112] Hwang D, Rust AG, Ramsey S, et al. (2005) A data integration methodology for systems biology. Proc Natl Acad Sci USA 102: 17296-17301.
    [113] Brügger B (2014) Lipidomics: Analysis of the lipid composition of cells and subcellular organelles by electrospray ionization mass spectrometry. Annu Rev Biochem 83: 79-98.
    [114] Yang K, Han X (2016) Lipidomics: techniques, applications, and outcomes related to biomedical sciences. Trends Biochem Sci 41: 954-969.
    [115] Merz K, Roux B (1996)  Biological Membranes. A Molecular Perspective from Computation and Experiment Birkhäuser (Basel): Springher.
    [116] Lombardo D, Calandra P, Pasqua L, et al. (2020) Self-assembly of organic nanomaterials and biomaterials: The bottom-up approach for functional nanostructures formation and advanced applications. Materials 13: 1048.
    [117] Calandra P (2020) On the physico-chemical basis of self-nanosegregation giving magnetically-induced birefringence in dibutyl phosphate/bis(2-ethylhexyl) amine systems. J Mol Liq 310: 113186.
    [118] Sachs JN, Petrache HI, Woolf TB (2003) Interpretation of small angle x-ray measurements guided by molecular dynamics simulations of lipid bilayers. Chem Phys Lipids 126: 211-223.
    [119] Pan J, Cheng X, Sharp M, et al. (2015) Structural and mechanical properties of cardiolipin lipid bilayers determined using neutron spin echo, small angle neutron and x-ray scattering, and molecular dynamics simulations. Soft Matter 11: 130-138.
    [120] Zhang G, Jiang H, Fan N (2018) Molecular dynamics simulation of cell membrane penetration by atomic force microscopy tip. Mod Phys Lett B 32: 1850198.
    [121] Ollila OHS, Pabst G (2016) Atomistic resolution structure and dynamics of lipid bilayers in simulations and experiments. Biochim Biophys Acta Biomembr 1858: 2512-2528.
    [122] Liu S, Xia T (2020) Continued efforts on nanomaterial-environmental health and safety is critical to maintain sustainable growth of nanoindustry. Small 16: 2000603.
    [123] Nigro A, Pellegrino M, Greco M, et al. (2018) Dealing with skin and blood-brain barriers: the unconventional challenges of mesoporous silica nanoparticles. Pharmaceutics 10: 250.
    [124] Salehi B, Calina D, Docea AO, et al. (2020) Curcumin's nanomedicine formulations for therapeutic application in neurological diseases. J Clin Med 9: 430.
    [125] Pasqua L, De Napoli IE, De Santo M, et al. (2019) Mesoporous silica-based hybrid materials for bone-specific drug delivery. Nanoscale Advances 1: 3269-3278.
  • Reader Comments
  • © 2020 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(823) PDF downloads(190) Cited by(1)

Article outline

Figures and Tables

Figures(6)

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog