Haemostasis pp 13-30 | Cite as

Platelet Physiology

  • Matthew D. Linden
Part of the Methods in Molecular Biology book series (MIMB, volume 992)


Platelets are cell fragments which circulate in blood. They are of pivotal importance in blood clot formation, affecting thrombosis and haemostasis. By rapidly altering the activation and expression of surface receptors, platelets are able to quickly undergo structural and phenotypic changes in response to stimulation, such as collagen exposure on injured vascular endothelium. This response to stimulation allows platelets to become adhesive, aggregate to form a thrombus, and release a variety of mediators affecting coagulation, inflammation, and chemotaxis at the site of injury. Therefore, in addition to their critical role in thrombosis and haemostasis, platelets also play a role in immunity, inflammation, wound healing, haematologic malignancies, and metabolic disorders. The role of platelets in disease, particularly in atherothrombosis, is increasingly the focus of current research and antiplatelet therapy plays a significant role in the prevention and treatment of atherothrombotic and inflammatory diseases.

Key words

Platelet physiology Platelet structure Granules Platelet activation Platelet receptors 


  1. 1.
    Hartwig JH (2002) Platelet structure. In: Michelson AD (ed) Platelets. Academic, San Diego, CA, pp 37–52Google Scholar
  2. 2.
    Boyles J, Fox JE, Phillips DR, Stenberg PE (1985) Organization of the cytoskeleton in resting, discoid platelets: preservation of actin filaments by a modified fixation that prevents osmium damage. J Cell Biol 101:1463–1472PubMedCrossRefGoogle Scholar
  3. 3.
    Reed GL (2002) Platelet secretion. In: Michelson AD (ed) Platelets. Academic, San Diego, CA, pp 181–195Google Scholar
  4. 4.
    Hartwig JH, DeSisto M (1991) The cytoskeleton of the resting human blood platelet: structure of the membrane skeleton and its attachment to actin filaments. J Cell Biol 112:407–425PubMedCrossRefGoogle Scholar
  5. 5.
    Tablin F, Reeber MJ, Nachmias VT (1988) Platelets contain a 210 K microtubule-associated protein related to a similar protein in HeLa cells. J Cell Sci 90(Pt 2):317–324PubMedGoogle Scholar
  6. 6.
    Kovacsovics TJ, Hartwig JH (1996) Thrombin-induced GPIb-IX centralization on the platelet surface requires actin assembly and myosin II activation. Blood 87:618–629PubMedGoogle Scholar
  7. 7.
    Schwer HD, Lecine P, Tiwari S, Italiano JE Jr, Hartwig JH, Shivdasani RA (2001) A lineage-restricted and divergent beta-tubulin isoform is essential for the biogenesis, structure and function of blood platelets. Curr Biol 11:579–586PubMedCrossRefGoogle Scholar
  8. 8.
    Shattil SJ, Hoxie JA, Cunningham M, Brass LF (1985) Changes in the platelet membrane glycoprotein IIb.IIIa complex during platelet activation. J Biol Chem 260:11107–11114PubMedGoogle Scholar
  9. 9.
    Berridge MJ (1984) Inositol trisphosphate and diacylglycerol as second messengers. Biochem J 220:345–360PubMedGoogle Scholar
  10. 10.
    Brass LF (1999) More pieces of the platelet activation puzzle slide into place. J Clin Invest 104:1663–1665PubMedCrossRefGoogle Scholar
  11. 11.
    Hartwig JH (1992) Mechanisms of actin rearrangements mediating platelet activation. J Cell Biol 118:1421–1442PubMedCrossRefGoogle Scholar
  12. 12.
    Carlier MF, Didry D, Erk I, Lepault J, Van Troys ML, Vandekerckhove J, Perelroizen I, Yin H, Doi Y, Pantaloni D (1996) Tbeta 4 is not a simple G-actin sequestering protein and interacts with F-actin at high concentration. J Biol Chem 271:9231–9239PubMedCrossRefGoogle Scholar
  13. 13.
    Knezevic I, Leisner TM, Lam SC (1996) Direct binding of the platelet integrin alphaIIbbeta3 (GPIIb-IIIa) to talin. Evidence that interaction is mediated through the cytoplasmic domains of both alphaIIb and beta3. J Biol Chem 271:16416–16421PubMedCrossRefGoogle Scholar
  14. 14.
    Niewiarowski S, Holt JC, Cook JJ (1994) Biochemistry and physiology of secreted platelet proteins. In: Coleman RW, Hirsh J, Marder VJ, Salzman EW (eds) Haemostasis and thrombosis: basic principles and clinical practice. Lippincott, Philidelphia, PA, pp 546–556Google Scholar
  15. 15.
    Fukami MH (1997) Dense granule factors. In: von Bruchhausen F, Walter U (eds) Platelets and their factors. Springer, New York, pp 419–432CrossRefGoogle Scholar
  16. 16.
    Knight DE, Hallam TJ, Scrutton MC (1982) Agonist selectivity and second messenger concentration in Ca2  +  -mediated secretion. Nature 296:256–257PubMedCrossRefGoogle Scholar
  17. 17.
    Chang JD, Ware JA (1997) Ca2+ and Protein Kinase C in Platelets. In: Bittar EE & Lapretina EG (eds) Advances in Molecular and Cell Biology Vol 18: The Platelet. JAI Press, Greenwich, pp 275–310Google Scholar
  18. 18.
    Shirakawa R, Yoshioka A, Horiuchi H, Nishioka H, Tabuchi A, Kita T (2000) Small GTPase Rab4 regulates Ca2  +  -induced alpha-granule secretion in platelets. J Biol Chem 275:33844–33849PubMedCrossRefGoogle Scholar
  19. 19.
    Nieuwland R, Sturk A (2002) Platelet-derived microparticles. In: Michelson AD (ed) Platelets. Academic, San Diego, CA, pp 255–265Google Scholar
  20. 20.
    Wiedmer T, Shattil SJ, Cunningham M, Sims PJ (1990) Role of calcium and calpain in complement-induced vesiculation of the platelet plasma membrane and in the exposure of the platelet factor Va receptor. Biochemistry 29:623–632PubMedCrossRefGoogle Scholar
  21. 21.
    Wiedmer T, Sims PJ (1991) Participation of protein kinases in complement C5b-9-induced shedding of platelet plasma membrane vesicles. Blood 78:2880–2886PubMedGoogle Scholar
  22. 22.
    Sims PJ, Faioni EM, Wiedmer T, Shattil SJ (1988) Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase activity. J Biol Chem 263:18205–18212PubMedGoogle Scholar
  23. 23.
    Sims PJ, Wiedmer T, Esmon CT, Weiss HJ, Shattil SJ (1989) Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant activity. J Biol Chem 264:17049–17057PubMedGoogle Scholar
  24. 24.
    Clemetson KJ (2002) Platelet receptors. In: Michelson AD (ed) Platelets. Academic, San Diego, CA, pp 65–84Google Scholar
  25. 25.
    Lopez JA, Berndt MC (2002) The GPIb-IX-V complex. In: Michelson AD (ed) Platelets. Academic, San Diego, CA, pp 85–104Google Scholar
  26. 26.
    Lopez JA (1994) The platelet glycoprotein Ib-IX complex. Blood Coagul Fibrinolysis 5:97–119PubMedCrossRefGoogle Scholar
  27. 27.
    Fredrickson BJ, Dong JF, McIntire LV, Lopez JA (1998) Shear-dependent rolling on von Willebrand factor of mammalian cells expressing the platelet glycoprotein Ib-IX-V complex. Blood 92:3684–3693PubMedGoogle Scholar
  28. 28.
    Ramakrishnan V, DeGuzman F, Bao M, Hall SW, Leung LL, Phillips DR (2001) A thrombin receptor function for platelet glycoprotein Ib-IX unmasked by cleavage of glycoprotein V. Proc Natl Acad Sci U S A 98:1823–1828PubMedCrossRefGoogle Scholar
  29. 29.
    Kroll MH, Hellums JD, McIntire LV, Schafer AI, Moake JL (1996) Platelets and shear stress. Blood 88:1525–1541PubMedGoogle Scholar
  30. 30.
    Simon DI, Chen Z, Xu H, Li CQ, Dong J, McIntire LV, Ballantyne CM, Zhang L, Furman MI, Berndt MC, Lopez JA (2000) Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med 192:193–204PubMedCrossRefGoogle Scholar
  31. 31.
    McEver RP (2006) P-Selectin/PSGL-1 and other interactions between platelets, leukocytes and endothelium. In: Michelson AD (ed) Platelets. Academic, San Diego, CA, pp 231–250Google Scholar
  32. 32.
    Kansas GS (1996) Selectins and the ligands: current concepts and controversies. Blood 88:3259–3287PubMedGoogle Scholar
  33. 33.
    Romo GM, Dong JF, Schade AJ, Gardiner EE, Kansas GS, Li CQ, McIntire LV, Berndt MC, Lopez JA (1999) The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin. J Exp Med 190:803–814PubMedCrossRefGoogle Scholar
  34. 34.
    Berndt MC, Phillips DR (1981) Interaction of thrombin with platelets: purification of the thrombin substrate. Ann N Y Acad Sci 370:87–95PubMedCrossRefGoogle Scholar
  35. 35.
    Baglia FA, Badellino KO, Li CQ, Lopez JA, Walsh PN (2002) Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin. J Biol Chem 277:1662–1668PubMedCrossRefGoogle Scholar
  36. 36.
    Hato T, Ginsberg MH, Shattil SJ (2002) Integrin alphallb-beta3. In: Michelson AD (ed) Platelets. Academic, San Diego, CA, pp 105–116Google Scholar
  37. 37.
    Cierniewski CS, Byzova T, Papierak M, Haas TA, Niewiarowska J, Zhang L, Cieslak M, Plow EF (1999) Peptide ligands can bind to distinct sites in integrin alphaIIbbeta3 and elicit different functional responses. J Biol Chem 274:16923–16932PubMedCrossRefGoogle Scholar
  38. 38.
    Tolentino AR, Bahou WF (2002) Thrombin receptors. In: Michelson AD (ed) Platelets. Academic, San Diego, CA, pp 117–138Google Scholar
  39. 39.
    Vu TK, Hung DT, Wheaton VI, Coughlin SR (1991) Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 64:1057–1068PubMedCrossRefGoogle Scholar
  40. 40.
    Rasmussen UB, Vouret-Craviari V, Jallat S, Schlesinger Y, Pages G, Pavirani A, Lecocq JP, Pouyssegur J, Van Obberghen-Schilling E (1991) cDNA cloning and expression of a hamster alpha-thrombin receptor coupled to Ca2+ mobilization. FEBS Lett 288:123–128PubMedCrossRefGoogle Scholar
  41. 41.
    Bizios R, Lai L, Fenton JW II, Malik AB (1986) Thrombin-induced chemotaxis and aggregation of neutrophils. J Cell Physiol 128:485–490PubMedCrossRefGoogle Scholar
  42. 42.
    Liu LW, Vu TK, Esmon CT, Coughlin SR (1991) The region of the thrombin receptor resembling hirudin binds to thrombin and alters enzyme specificity. J Biol Chem 266:16977–16980PubMedGoogle Scholar
  43. 43.
    Vu TK, Wheaton VI, Hung DT, Charo I, Coughlin SR (1991) Domains specifying thrombin-receptor interaction. Nature 353:674–677PubMedCrossRefGoogle Scholar
  44. 44.
    Ishihara H, Connolly AJ, Zeng D, Kahn ML, Zheng YW, Timmons C, Tram T, Coughlin SR (1997) Protease-activated receptor 3 is a second thrombin receptor in humans. Nature 386:502–506PubMedCrossRefGoogle Scholar
  45. 45.
    Xu W-F, Anderson H, Whitmore TE, Presnell SR, Yee DP, Ching AC, Gilbert T, Davie EW, Foster DC (1998) Cloning and characterization of the human protease-activated receptor 4. Proc Natl Acad Sci U S A 95:6642–6646PubMedCrossRefGoogle Scholar
  46. 46.
    Brass LF, Manning DR, Cichowski K, Abrams CS (1997) Signaling through G proteins in platelets: to the integrins and beyond. Thromb Haemost 78:581–589PubMedGoogle Scholar
  47. 47.
    Brass LF (1997) Thrombin receptor antagonists: a work in progress. Coron Artery Dis 8:49–58PubMedCrossRefGoogle Scholar
  48. 48.
    Ayyanathan K, Webbs TE, Sandhu AK, Athwal RS, Barnard EA, Kunapuli SP (1996) Cloning and chromosomal localization of the human P2Y1 purinoceptor. Biochem Biophys Res Commun 218:783–788PubMedCrossRefGoogle Scholar
  49. 49.
    Hollopeter G, Jantzen H-M, Vincent D, Li G, England L, Ramakrishnan V, Yang R-B, Nurden P, Nurden A, Julius D, Conley PB (2001) Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 409:202–207PubMedCrossRefGoogle Scholar
  50. 50.
    Jin J, Kunapuli SP (1998) Coactivation of two different G protein-coupled receptors is essential for ADP-induced platelet aggregation. Proc Natl Acad Sci U S A 95:8070–8074PubMedCrossRefGoogle Scholar
  51. 51.
    Kehrel B, Wierwille S, Clemetson KJ, Anders O, Steiner M, Knight CG, Farndale RW, Okuma M, Barnes MJ (1998) Glycoprotein VI is a major collagen receptor for platelet activation: it recognizes the platelet-activating quaternary structure of collagen, whereas CD36, glycoprotein IIb/IIIa, and von Willebrand factor do not. Blood 91:491–499PubMedGoogle Scholar
  52. 52.
    Woulfe D, Yang J, Prevost N, O’Brien P, Brass LF (2002) Signal transduction during the initiation, extension, and perpetuation of platelet plug formation. In: Michelson AD (ed) Platelets. Academic, San Diego, CA, pp 197–213Google Scholar
  53. 53.
    Hung DT, Wong YH, Vu TK, Coughlin SR (1992) The cloned platelet thrombin receptor couples to at least two distinct effectors to stimulate phosphoinositide hydrolysis and inhibit adenylyl cyclase. J Biol Chem 267:20831–20834PubMedGoogle Scholar
  54. 54.
    Hung DT, Vu TH, Nelken NA, Coughlin SR (1992) Thrombin-induced events in non-platelet cells are mediated by the unique proteolytic mechanism established for the cloned platelet thrombin receptor. J Cell Biol 116:827–832PubMedCrossRefGoogle Scholar
  55. 55.
    Klages B, Brandt U, Simon MI, Schultz G, Offermanns S (1999) Activation of G12/G13 results in shape change and Rho/Rho-kinase-mediated myosin light chain phosphorylation in mouse platelets. J Cell Biol 144:745–754PubMedCrossRefGoogle Scholar
  56. 56.
    Shattil SJ (1999) Signaling through platelet integrin alpha IIb beta 3: inside-out, outside-in, and sideways. Thromb Haemost 82:318–325PubMedGoogle Scholar
  57. 57.
    Barnard MR, Linden MD, Frelinger AL III, Li Y, Fox ML, Furman MI, Michelson AD (2005) Effects of platelet binding on whole blood flow cytometry assays of monocyte and neutrophil procoagulant activity. J Thromb Haemost 3:2563–2570PubMedCrossRefGoogle Scholar
  58. 58.
    Libby P, Simon DI (2001) Inflammation and thrombosis: the clot thickens. Circulation 103:1718–1720PubMedCrossRefGoogle Scholar
  59. 59.
    McEver RP (2002) P-selectin/PSGL-1 and other interactions between platelets, leukocytes, and endothelium. In: Michelson AD (ed) Platelets. Academic, San Diego, CA, pp 139–155Google Scholar
  60. 60.
    Palabrica T, Lobb R, Furie BC, Aronovitz M, Benjamin C, Hsu YM, Sajer SA, Furie B (1992) Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets. Nature 359:848–851PubMedCrossRefGoogle Scholar
  61. 61.
    Huo Y, Schober A, Forlow SB, Smith DF, Hyman MC, Jung S, Littman DR, Weber C, Ley K (2003) Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nat Med 9:61–67PubMedCrossRefGoogle Scholar
  62. 62.
    Schonbeck U, Libby P (2001) CD40 signaling and plaque instability. Circ Res 89:1092–1103PubMedCrossRefGoogle Scholar
  63. 63.
    Schonbeck U, Libby P (2001) The CD40/CD154 receptor/ligand dyad. Cell Mol Life Sci 58:4–43PubMedCrossRefGoogle Scholar
  64. 64.
    Furman MI, Benoit SE, Barnard MR, Valeri CR, Borbone ML, Becker RC, Hechtman HB, Michelson AD (1998) Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease. J Am Coll Cardiol 31:352–358PubMedCrossRefGoogle Scholar
  65. 65.
    Ott I, Neumann FJ, Gawaz M, Scmitt M, Schomig A (1996) Increased neutrophil-platelet adhesion in patients with unstable angina. Circulation 94:1239–1246PubMedCrossRefGoogle Scholar
  66. 66.
    Michelson AD, Barnard MR, Krueger LA, Valeri CR, Furman MI (2001) Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin: studies in baboons, human coronary intervention, and human acute myocardial infarction. Circulation 104:1533–1537PubMedCrossRefGoogle Scholar
  67. 67.
    Mickelson JK, Lakkis NM, Villarreal-Levy G, Hughes BJ, Smith CW (1996) Leukocyte activation with platelet adhesion after coronary angioplasty: a mechanism for recurrent disease? J Am Coll Cardiol 28:345–353PubMedCrossRefGoogle Scholar
  68. 68.
    Michelson AD, Linden MD, Barnard MR, Furman MI, Frelinger AL (2006) Flow Cytometry. In: Michelson AD (ed) Platelets. Academic Press, San Diego, CA, pp 545–565Google Scholar
  69. 69.
    Hsu-Lin SC, Berman CL, Furie BC, August D, Furie B (1984) A platelet membrane protein expressed during platelet activation and secretion: studies using a monoclonal antibody specific for thrombin-activated platelets. J Biol Chem 259:9121–9126PubMedGoogle Scholar
  70. 70.
    Stenberg PE, McEver RP, Shuman MA, Jacques YV, Bainton DF (1985) A platelet alpha-granule membrane protein (GMP-140) is expressed on the platelet membrane after activation. J Cell Biol 101:880–886PubMedCrossRefGoogle Scholar
  71. 71.
    Michelson AD, Benoit SE, Kroll MH, Li J, Rohrer MJ, Kestin AS, Barnard MR (1994) The activation-induced decrease in the platelet surface expression of the glycoprotein Ib-IX complex is reversible. Blood 83:3562–3573PubMedGoogle Scholar
  72. 72.
    Ruf A, Patscheke H (1995) Flow cytometric detection of activated platelets: comparison of determining shape change, fibrinogen binding, and P-selectin expression. Semin Thromb Hemost 21:146–151PubMedCrossRefGoogle Scholar
  73. 73.
    Michelson AD, Barnard MR, Hechtman HB, MacGregor H, Connolly RJ, Loscalzo J, Valeri CR (1996) In vivo tracking of platelets: circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function. Proc Natl Acad Sci U S A 93:11877–11882PubMedCrossRefGoogle Scholar
  74. 74.
    Larsen E, Celi A, Gilbert GE, Furie BC, Erban JK, Bonfanti R, Wagner DD, Furie B (1989) PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell 59:305–312PubMedCrossRefGoogle Scholar
  75. 75.
    Hamburger SA, McEver RP (1990) GMP-140 mediates adhesion of stimulated platelets to neutrophils. Blood 75:550–554PubMedGoogle Scholar
  76. 76.
    Linden MD, Furman MI (2005) Monocyte-platelet aggregates in patients with ischemic heart disease. In: Morrow DA, Cannon C (eds) Cardiovascular biomarkers: pathophysiology and disease management. Humana, Totowa, NJ, pp 487–493Google Scholar
  77. 77.
    Hidari KI, Weyrich AS, Zimmerman GA, McEver RP (1997) Engagement of P-selectin glycoprotein ligand-1 enhances tyrosine phosphorylation and activates mitogen-activated protein kinases in human neutrophils. J Biol Chem 272:28750–28756PubMedCrossRefGoogle Scholar
  78. 78.
    Blanks JE, Moll T, Eytner R, Vestweber D (1998) Stimulation of P-selectin glycoprotein ligand-1 on mouse neutrophils activates beta 2-integrin mediated cell attachment to ICAM-1. Eur J Immunol 28:433–443PubMedCrossRefGoogle Scholar
  79. 79.
    Evangelista V, Manarini S, Sideri R, Rotondo S, Martelli N, Piccoli A, Totani L, Piccardoni P, Vestweber D, de Gaetano G, Cerletti C (1999) Platelet/polymorphonuclear leukocyte interaction: P-selectin triggers protein-tyrosine phosphorylation-dependent CD11b/CD18 adhesion: role of PSGL-1 as a signaling molecule. Blood 93:876–885PubMedGoogle Scholar
  80. 80.
    Weber C, Springer TA (1997) Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor. J Clin Invest 100:2085–2093PubMedCrossRefGoogle Scholar
  81. 81.
    Weyrich AS, Elstad MR, McEver RP, McIntyre TM, Moore KL, Morrissey JH, Prescott SM, Zimmerman GA (1996) Activated platelets signal chemokine synthesis by human monocytes. J Clin Invest 97:1525–1534PubMedCrossRefGoogle Scholar
  82. 82.
    Ostrovsky L, King AJ, Bond S, Mitchell D, Lorant DE, Zimmerman GA, Larsen R, Niu XF, Kubes P (1998) A juxtacrine mechanism for neutrophil adhesion on platelets involves platelet-activating factor and a selectin-dependent activation process. Blood 91:3028–3036PubMedGoogle Scholar
  83. 83.
    Diacovo TG, deFougerolles AR, Bainton DF, Springer TA (1994) A functional integrin ligand on the surface of platelets: intercellular adhesion molecule-2. J Clin Invest 94:1243–1251PubMedCrossRefGoogle Scholar
  84. 84.
    Rinder HM, Bonan JL, Rinder CS, Ault KA, Smith BR (1991) Dynamics of leukocyte-platelet adhesion in whole blood. Blood 78:1730–1737PubMedGoogle Scholar
  85. 85.
    Frenette PS, Denis CV, Weiss L, Jurk K, Subbarao S, Kehrel B, Hartwig JH, Vestweber D, Wagner DD (2000) P-Selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo. J Exp Med 191:1413–1422PubMedCrossRefGoogle Scholar
  86. 86.
    Andre P, Denis CV, Ware J, Saffaripour S, Hynes RO, Ruggeri ZM, Wagner DD (2000) Platelets adhere to and translocate on von Willebrand factor presented by endothelium in stimulated veins. Blood 96:3322–3328PubMedGoogle Scholar
  87. 87.
    Bombeli T, Schwartz BR, Harlan JM (1998) Adhesion of activated platelets to endothelial cells: evidence for a GPIIbIIIa-dependent bridging mechanism and novel roles for endothelial intercellular adhesion molecule 1 (ICAM-1), alphavbeta3 integrin, and GPIbalpha. J Exp Med 187:329–339PubMedCrossRefGoogle Scholar
  88. 88.
    Bouchard BA, Butenas S, Mann KG, Tracy PB (2002) Interactions between platelets and the coagulation system. In: Michelson AD (ed) Platelets. Academic, San Diego, CA, pp 229–253Google Scholar

Copyright information

© Humana Press 2013

Authors and Affiliations

  • Matthew D. Linden
    • 1
  1. 1.Centre for Microscopy, Characterisation and AnalysisUniversity of Western AustraliaCrawleyAustralia

Personalised recommendations