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Engineered Nanoparticles Induced Brush Border Disruption in a Human Model of the Intestinal Epithelium

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Nanomaterial

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 811))

Abstract

Nanoparticles hold great promise in cell biology and medicine due to the inherent physico-chemical properties when these materials are synthesized on the nanoscale. Moreover, their small size, and the ability to functionalize the outer nanoparticle surface makes them an ideal vector suited to traverse a number of physical barriers in the human body. While nanoparticles hold great promise for applications in cell biology and medicine, their downfall is the toxicity that accompanies exposure to biological systems. This chapter focuses on exposure via the oral route since nanomaterials are being engineered to act as carriers for drugs, contrast agents for specialized imaging techniques, as well as ingested pigments approved by regulatory agencies for human food products. After these nanomaterials are ingested they have the potential to interact with a number of biologically significant tissues, one of which is the epithelium of the small intestine. Within the small intestine exists enterocytes whose principal function is nutrient absorption. The absorptive process is aided by microvilli that act to increase the surface area of the epithelium. Dense arrays of microvilli, referred to as the brush border, have recently been shown to undergo disruption as a consequence of exposure to nanomaterials. This chapter aims to set the stage for detailed mechanistic studies at the cell biology level concerning this newly emerging nanotoxicity research paradigm, as the underlying structural characterization responsible for the existence of microvilli have been elucidated.

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References

  1. Dunphy Guzman KA, Taylor MR, Banfield JF (2006) Environmental risks of nanotechnology: national nanotechnology initiative funding, 2000–2004. Environ Sci Technol 40:1401–1407

    Article  CAS  Google Scholar 

  2. Foss Hansen S, Larsen BH, Olsen SI, Baun A (2007) Categorization framework to aid hazard identification of nanomaterials. Nanotoxicology 1:243–250

    Article  Google Scholar 

  3. Arruebo M, Fernández-Pacheco R, Ibarra MR, Santamaría J (2007) Magnetic nanoparticles for drug delivery. Nano Today 2:22–32

    Article  Google Scholar 

  4. Mahmoudi M, Sant S, Wang B, Laurent S, Sen T (2011) Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modification and applications in chemotherapy. Adv Drug Deliv Rev 63:24–46

    Article  CAS  PubMed  Google Scholar 

  5. Oh JK, Park JM (2011) Iron oxide-based superparamagnetic polymeric nanomaterials: design, preparation, and biomedical application. Prog Polym Sci 36:168–189

    Article  CAS  Google Scholar 

  6. Howarth M, Takao K, Hayashi Y, Ting AY (2005) Targeting quantum dots to surface proteins in living cells with biotin ligase. Proc Natl Acad Sci U S A 102:7583–7588

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Resch-Genger U, Grabolle M, Cavaliere-Jaricot S, Nitschke R, Nann T (2008) Quantum dots versus organic dyes as fluorescent labels. Nat Methods 5:763–775

    Article  CAS  PubMed  Google Scholar 

  8. Gao X, Cui Y, Levenson RM, Chung LW, Nie S (2004) In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 22:969–976

    Article  CAS  PubMed  Google Scholar 

  9. Huang H-C, Rege K, Heys JJ (2010) Spatiotemporal temperature distribution and cancer cell death in response to extracellular hyperthermia induced by gold nanorods. ACS Nano 4:2892–2900

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Sylvester P, Westerhoff P, Möller T, Badruzzaman M, Boyd O (2007) A hybrid sorbent utilizing nanoparticles of hydrous iron oxide for arsenic removal from drinking water. Environ Eng Sci 24:104–112

    Article  CAS  Google Scholar 

  11. Donaldson K, Seaton A (2012) A short history of the toxicology of inhaled particles. Part Fibre Toxicol 9:13

    Article  PubMed Central  PubMed  Google Scholar 

  12. Mukherjee T, Williams AW (1967) A comparative study of the ultrastructure of microvilli in the epithelium of small and large intestine of mice. J Cell Biol 34:447–461

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Misch D, Giebel P, Faust R (1980) Intestinal microvilli: responses to feeding and fasting. Eur J Cell Biol 21:269–279

    CAS  PubMed  Google Scholar 

  14. Stidwill RP, Wysolmerski T, Burgess DR (1984) The brush border cytoskeleton is not static: in vivo turnover of proteins. J Cell Biol 98:641–645

    Article  CAS  PubMed  Google Scholar 

  15. Granger B, Baker RF (1950) Electron microscope investigation of the striated border of intestinal epithelium. Anat Rec 107:423–441

    Article  CAS  PubMed  Google Scholar 

  16. Miller D, Crane RK (1961) The digestive function of the epithelium of the small intestine: II. Localization of disaccharide hydrolysis in the isolated brush border portion of intestinal epithelial cells. Biochim Biophys Acta 52:293–298

    Article  CAS  PubMed  Google Scholar 

  17. Palay SL, Karlin LJ (1959) An electron microscopic study of the intestinal villus. I. The fasting animal. J Biophys Biochem Cytol 5:363–371

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Trier JS (1963) Studies on small intestinal crypt epithelium. I. The fine structure of the crypt epithelium of the proximal small intestine of fasting humans. J Cell Biol 18:599–620

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. McNabb J, Sandborn E (1964) Filaments in the microvillous border of intestinal cells. J Cell Biol 22:701–704

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Ishikawa H, Bischoff R, Holtzer H (1969) Formation of arrowhead complexes with heavy meromyosin in a variety of cell types. J Cell Biol 43:312–328

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Tilney LG, Mooseker M (1971) Actin in the brush-border of epithelial cells of the chicken intestine. Proc Natl Acad Sci U S A 68:2611–2615

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Arpin M, Friederich E (1992) Cytoskeletal components in intestinal brush border morphogenesis: an evaluation of their function. In: Fleming TP (ed) Epithelial organization and development. Dordrecht, Springer

    Google Scholar 

  23. Bretscher A (1983) Microfilament organization in the cytoskeleton of the intestinal brush border. Cell Muscle Motil 4:239

    CAS  PubMed  Google Scholar 

  24. Coudrier E, Kerjaschki D, Louvard D (1988) Cytoskeleton organization and submembranous interactions in intestinal and renal brush borders. Kidney Int 34:309

    Article  CAS  PubMed  Google Scholar 

  25. Hirokawa N, Tilney LG, Fujiwara K, Heuser JE (1982) Organization of actin, myosin, and intermediate filaments in the brush border of intestinal epithelial cells. J Cell Biol 94:425–443

    Article  CAS  PubMed  Google Scholar 

  26. Mooseker MS (1985) Organization, chemistry, and assembly of the cytoskeletal apparatus of the intestinal brush border. Annu Rev Cell Biol 1:209–241

    Article  CAS  PubMed  Google Scholar 

  27. Shibayama T, Carboni JM, Mooseker MS (1987) Assembly of the intestinal brush border: appearance and redistribution of microvillar core proteins in developing chick enterocytes. J Cell Biol 105:335–344

    Article  CAS  PubMed  Google Scholar 

  28. Bement WM, Mooseker MS (1996) The cytoskeleton of the intestinal epithelium: components, assembly, and dynamic rearrangements. In: Hesketh E, Pryme JF (eds) The cytoskeleton: a multi-volume treatise, vol 3. JAI Press, Greenwich, pp 359–404

    Google Scholar 

  29. Heintzelman MB, Mooseker MS (1992) Assembly of the intestinal brush border cytoskeleton. Curr Top Dev Biol 26:93–122

    Article  CAS  PubMed  Google Scholar 

  30. Begg DA, Rodewald R, Rebhun LI (1978) The visualization of actin filament polarity in thin sections. Evidence for the uniform polarity of membrane-associated filaments. J Cell Biol 79:846–852

    Article  CAS  PubMed  Google Scholar 

  31. Hirokawa N, Heuser JE (1981) Quick-freeze, deep-etch visualization of the cytoskeleton beneath surface differentiations of intestinal epithelial cells. J Cell Biol 91:399–409

    Article  CAS  PubMed  Google Scholar 

  32. Bretscher A, Weber K (1980) Fimbrin, a new microfilament-associated protein present in microvilli and other cell surface structures. J Cell Biol 86:335–340

    Article  CAS  PubMed  Google Scholar 

  33. Bretscher A, Weber K (1980) Villin is a major protein of the microvillus cystoskeleton which binds both G and F actin in a calcium-dependent manner. Cell 20:839–847

    Article  CAS  PubMed  Google Scholar 

  34. Bartles JR, Zheng L, Li A, Wierda A, Chen B (1998) Small espin: a third actin-bundling protein and potential forked protein ortholog in brush border microvilli. J Cell Biol 143:107–119

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Garcia A, Coudrier E, Carboni J, Anderson J, Vandekerkhove J, Mooseker M, Louvard D, Arpin M (1989) Partial deduced sequence of the 110-kD-calmodulin complex of the avian intestinal microvillus shows that this mechanoenzyme is a member of the myosin I family. J Cell Biol 109:2895–2903

    Article  CAS  PubMed  Google Scholar 

  36. Glenney JR, Osborn M, Weber K (1982) The intracellular localization of the microvillus 110 K protein, a component considered to be involved in side-on membrane attachment of F-actin. Exp Cell Res 138:199–205

    Article  CAS  PubMed  Google Scholar 

  37. Howe CL, Mooseker MS (1983) Characterization of the 110-kdalton actin-calmodulin-, and membrane-binding protein from microvilli of intestinal epithelial cells. J Cell Biol 97:974–985

    Article  CAS  PubMed  Google Scholar 

  38. Berryman M, Franck Z, Bretscher A (1993) Ezrin is concentrated in the apical microvilli of a wide variety of epithelial cells whereas moesin is found primarily in endothelial cells. J Cell Sci 105:1025–1043

    CAS  PubMed  Google Scholar 

  39. Bretscher A (1983) Purification of an 80,000-dalton protein that is a component of the isolated microvillus cytoskeleton, and its localization in nonmuscle cells. J Cell Biol 97:425–432

    Article  CAS  PubMed  Google Scholar 

  40. Bretscher A, Reczek D, Berryman M (1997) Ezrin: a protein requiring conformational activation to link microfilaments to the plasma membrane in the assembly of cell surface structures. J Cell Sci 110:3011–3018

    CAS  PubMed  Google Scholar 

  41. Brown JW, Mcknight CJ (2010) Molecular model of the microvillar cytoskeleton and organization of the brush border. PLoS One 5:e9406

    Article  PubMed Central  PubMed  Google Scholar 

  42. D’Angelo R, Aresta S, Blangy A, del Maestro L, Louvard D, Arpin M (2007) Interaction of ezrin with the novel guanine nucleotide exchange factor PLEKHG6 promotes RhoG-dependent apical cytoskeleton rearrangements in epithelial cells. Mol Biol Cell 18:4780–4793

    Article  PubMed Central  PubMed  Google Scholar 

  43. Zwaenepoel I, Naba A, da Cunha MML, del Maestro L, Formstecher E, Louvard D, Arpin M (2012) Ezrin regulates microvillus morphogenesis by promoting distinct activities of Eps8 proteins. Mol Biol Cell 23:1080–1095

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Glenney JR, Glenney P, Weber K (1983) The spectrin-related molecule, TW-260/240, cross-links the actin bundles of the microvillus rootlets in the brush borders of intestinal epithelial cells. J Cell Biol 96:1491–1496

    Article  CAS  PubMed  Google Scholar 

  45. Hirokawa N, Cheney RE, Willard M (1983) Location of a protein of the fodrin-spectrin-TW260/240 family in the mouse intestinal brush border. Cell 32:953–965

    Article  CAS  PubMed  Google Scholar 

  46. Mooseker MS (1976) Brush border motility. Microvillar contraction in triton-treated brush borders isolated from intestinal epithelium. J Cell Biol 71:417–433

    Article  CAS  PubMed  Google Scholar 

  47. Bretscher A, Weber K (1978) Localization of actin and microfilament-associated proteins in the microvilli and terminal web of the intestinal brush border by immunofluorescence microscopy. J Cell Biol 79:839–845

    Article  CAS  PubMed  Google Scholar 

  48. Grimm-Günter E-MS, Revenu C, Ramos S, Hurbain I, Smyth N, Ferrary E, Louvard D, Robine S, Rivero F (2009) Plastin 1 binds to keratin and is required for terminal web assembly in the intestinal epithelium. Mol Biol Cell 20:2549–2562

    Article  PubMed Central  PubMed  Google Scholar 

  49. Achler C, Filmer D, Merte C, Drenckhahn D (1989) Role of microtubules in polarized delivery of apical membrane proteins to the brush border of the intestinal epithelium. J Cell Biol 109:179–189

    Article  CAS  PubMed  Google Scholar 

  50. Gilbert T, le Bivic A, Quaroni A, Rodriguez-Boulan E (1991) Microtubular organization and its involvement in the biogenetic pathways of plasma membrane proteins in Caco-2 intestinal epithelial cells. J Cell Biol 113:275–288

    Article  CAS  PubMed  Google Scholar 

  51. Halbleib JM, Sääf AM, Brown PO, Nelson WJ (2007) Transcriptional modulation of genes encoding structural characteristics of differentiating enterocytes during development of a polarized epithelium in vitro. Mol Biol Cell 18:4261–4278

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Monopoli MP, Åberg C, Salvati A, Dawson KA (2012) Biomolecular coronas provide the biological identity of nanosized materials. Nat Nanotechnol 7:779–786

    Article  CAS  PubMed  Google Scholar 

  53. Wang B, Zhang L, Bae SC, Granick S (2008) Nanoparticle-induced surface reconstruction of phospholipid membranes. Proc Natl Acad Sci U S A 105:18171–18175

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. de Beauregard MC, Pringault E, Robine S, Louvard D (1995) Suppression of villin expression by antisense RNA impairs brush border assembly in polarized epithelial intestinal cells. EMBO J 14:409

    Google Scholar 

  55. Koeneman BA, Zhang Y, Westerhoff P, Chen Y, Crittenden JC, Capco DG (2010) Toxicity and cellular responses of intestinal cells exposed to titanium dioxide. Cell Biol Toxicol 26:225–238

    Article  CAS  PubMed  Google Scholar 

  56. Fisichella M, Berenguer F, Steinmetz G, Auffan M, Rose J, Prat O (2012) Intestinal toxicity evaluation of TiO2 degraded surface-treated nanoparticles: a combined physico-chemical and toxicogenomics approach in Caco-2 cells. Part Fibre Toxicol 9:18

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Virkutyte J, Al-Abed SR, Dionysiou DD (2012) Depletion of the protective aluminum hydroxide coating in TiO2-based sunscreens by swimming pool water ingredients. Chem Eng J 191:95–103

    Article  CAS  Google Scholar 

  58. Kalive M, Zhang W, Chen Y, Capco DG (2012) Human intestinal epithelial cells exhibit a cellular response indicating a potential toxicity upon exposure to hematite nanoparticles. Cell Biol Toxicol 28:343–368

    Article  CAS  PubMed  Google Scholar 

  59. Zhang W, Kalive M, Capco DG, Chen Y (2010) Adsorption of hematite nanoparticles onto Caco-2 cells and the cellular impairments: effect of particle size. Nanotechnology 21:355103

    Article  PubMed  Google Scholar 

  60. Temm-Grove C, Helbing D, Wiegand C, Honer B, Jockusch B (1992) The upright position of brush border-type microvilli depends on myosin filaments. J Cell Sci 101:599–610

    CAS  PubMed  Google Scholar 

  61. Weir A, Westerhoff P, Fabricius L, Hristovski K, Von Goetz N (2012) Titanium dioxide nanoparticles in food and personal care products. Environ Sci Technol 46:2242–2250

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. FDA, U (2010) Summary of color additives listed for use in the United States in food, drugs, cosmetics, and medical devices. Color additives approved for use in cosmetics part 73, subpart C: Color additives exempt from batch certification, United States Food and Drug Administration

    Google Scholar 

  63. Freshney RI (2005) Culture of specific cell types. Wiley-Blackwell. http://bcs.wiley.com/he-bcs/Books?action=index&bcsId=5959&itemId=0470528125

  64. Artursson P, Palm K, Luthman K (2001) Caco-2 monolayers in experimental and theoretical predictions of drug transport.” Adv Drug Deliv Rev 46.1:27–43

    Google Scholar 

  65. Hidalgo IJ, Raub TJ, Borchardt RT (1989) Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology 96:736–749

    CAS  PubMed  Google Scholar 

  66. Bement WM, Forscher P, Mooseker MS (1993) A novel cytoskeletal structure involved in purse string wound closure and cell polarity maintenance. J Cell Biol 121:565–578

    Article  CAS  PubMed  Google Scholar 

  67. Faust J, Capco D (2012) Multifunctional scaffolds in eggs: sites for localization, signal transduction and meiotic spindle polarity. Front Biosci (Schol Ed) 5:496–506

    Google Scholar 

  68. Koeneman BA, Zhang Y, Hristovski K, Westerhoff P, Chen Y, Crittenden JC, Capco DG (2009) Experimental approach for an <i> in vitro </i> toxicity assay with non-aggregated quantum dots. Toxicol In Vitro 23:955–962

    Article  CAS  PubMed  Google Scholar 

  69. Peterson MD, Bement WM, Mooseker MS (1993) An in vitro model for the analysis of intestinal brush border assembly. II. Changes in expression and localization of brush border proteins during cell contact-induced brush border assembly in Caco-2BBe cells. J Cell Sci 105:461–472

    CAS  PubMed  Google Scholar 

  70. Oberdörster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D (2005) Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2:8

    Article  PubMed Central  PubMed  Google Scholar 

  71. Faust JJ, Zhang W, Koeneman BA, Chen Y, Capco DG (2012) Commenting on the effects of surface treated-and non-surface treated TiO2 in the Caco-2 cell model. Part Fibre Toxicol 9:42

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Peterson MD, Mooseker MS (1993) An in vitro model for the analysis of intestinal brush border assembly. I. Ultrastructural analysis of cell contact-induced brush border assembly in Caco-2BBe cells. J Cell Sci 105:445–460

    PubMed  Google Scholar 

  73. Passey S, Pellegrin S, Mellor H (2007) Scanning electron microscopy of cell surface morphology. Curr Protoc Cell Biol 4–17

    Google Scholar 

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Correspondence to David G. Capco .

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Faust, J.J., Masserano, B.M., Mielke, A.H., Abraham, A., Capco, D.G. (2014). Engineered Nanoparticles Induced Brush Border Disruption in a Human Model of the Intestinal Epithelium. In: Capco, D., Chen, Y. (eds) Nanomaterial. Advances in Experimental Medicine and Biology, vol 811. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8739-0_4

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