Artificial Cells with Ultrathin Lipid-Polymer or Lipid-Protein Membranes

  • T. M. S. Chang
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 238)


Cell membranes consist of phospholipid-cholesterol bilayer with other components incorporated. In addition, there is a “skeletal” protein structure supporting the bilayer. This “skeletal” protein structure is very important in the case of red blood cells. It retains the shape and integrity of the red blood cell membrane. The first artificial cells prepared have membranes of cross-linked protein or synthetic polymers (Chang, 1957, 1964). Later, a single bilayer of phospholipid-cholesterol is added to the outside of the cross-linked protein membrane or polymer membrane (Chang, 1969a, 1972b). These artificial cells with lipid-protein membrane resembles more closely biological cells. The use of ultrathin lipid-polymer membranes for artificial cells results in stronger membranes. The flux for sodium and rubidium across these artificial cells is the same as for red blood cells (Chang, 1969a, 1972b, Rosenthal and Chang, 1980). Furthermore, addition of valinomycin to the suspension increases influx for rubidium without any change in sodium influx (Rosenthal and Chang, 1980). The following is an updated method for the preparation of lipid-polymer membrane artificial cells (Yu and Chang, 1982; Chang, 1985, 1987, Ilan and Chang, 1986).


Immobilize Enzyme Glucose Dehydrogenase Artificial Cell Blood Substitute Multienzyme System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bourget, L. and Chang, T.M.S., 1984, Artificial cell-microencapsulated phenylalanine ammonia lyase, J. Appl. Biochem. & Biotechnol., 10:57–59.Google Scholar
  2. Bourget, L. and Chang, T.M.S., 1985, Phenylalanine ammonia-lysase immobilized in semipermeable microcapsules for enzyme replacement in phenylketonuria, FEBS Letters, 180:5–8.PubMedGoogle Scholar
  3. Bourget, L. and Chang, T.M.S., 1986, Phenylalanine ammonia-lyase immobilized in microcapsules for the depleture of phenylalanine in plasma in Phenylketonuric rat model, Biochim. Biophys. Acta, 883:432–438.PubMedGoogle Scholar
  4. Chang, T.M.S., 1957, Hemoglobin corpuscles, report of research project for B.Sc. Honours, McGill University.Google Scholar
  5. Chang, T.M.S., 1964, Semipermeable microcapsules, Science, 146:524–525.PubMedGoogle Scholar
  6. Chang, T.M.S., 1965, Semipermeable aqueous microcapsules, Ph.D. thesis, McGill University.Google Scholar
  7. Chang, T.M.S., 1966, Semipermeable aqueous microcapsules (“artificial cells”): with emphasis on experiments in an extracorporeal shunt system, Trans. Amer. Soc. Artif. Intern. Organs. 12:13–19.Google Scholar
  8. Chang, T.M.S., 1969a, Lipid-coated spherical ultrathin membranes of polymer or cross-linked protein as possible cell membrane models, Federation Proc., 28:461.Google Scholar
  9. Chang, T.M.S., 1969b, Clinical potential of enzyme technology, Science Tools, 16:33–39.Google Scholar
  10. Chang, T.M.S., 1970, “Nonthrombogenic Microcapsules”, U.S. Patent, 3,522,346.Google Scholar
  11. Chang, T.M.S., 1971a, Stabilization of enzymes by microencapsulation with a concentrated protein solution or by microencapsulation followed by cross-linking with glutaraldehyde, Biochem. Biophys. Res. Commun., 44:1531–1536.PubMedGoogle Scholar
  12. Chang, T.M.S., 1971b, The in-vivo effects of semipermeable microcapsules containing L-asparaginase on 6C3HED lymphosarcoma, Nature, 229(528):117–118.PubMedGoogle Scholar
  13. Chang, T.M.S., 1972a, “Artificial Cells”, Thomas, Springfield, IL.Google Scholar
  14. Chang, T M.S., 1972b, A new approach to separation using semipermeable microcapsules (artificial cells): combined dialysis, catalysis, and absorption, in: “Recent Development in Separation Science”, N.N. Li, ed., CRC Press, Cleveland, OH, Vol. 1, pp. 203–216.Google Scholar
  15. Chang, T.M.S., 1973a, L-Asparaginase immobilized within semipermeable microcapsules: in-vitro and in-vivo stability, Enzyme, 14(2):95–104.Google Scholar
  16. Chang, T.M.S., 1974a, A comparison of semipermeable microcapsules and standard dialysers for use in separation, Separ. Purif. Methods, 3:245–262.Google Scholar
  17. Chang, T.M.S., 1975a, Artificial cells, Chem. Techn., 5:80–85.Google Scholar
  18. Chang, T.M.S., 1975b, Microencapsulated adsorbent hemoperfusion for uremia, intoxication and hepatic failure, Kidney Intl., 7:S387–392.Google Scholar
  19. Chang, T.M.S., 1975c, The one shot vaccine, in: “Socio-Economic and Ethical Implications of Enzyme Engineering”, International Federation of Institutes for Advanced Studies, C.-G. Heden, ed., Stockholm, Sweden, pp. 17–18.Google Scholar
  20. Chang, T.M.S., 1975d, Artificial cells as carriers for biologically active materials in therapy, in: “Clinical Pharmacology”, M. J. Mattila, ed., Vol. 5, Proc. 6th International Congress of Pharmacology, Finland, pp. 81–90.Google Scholar
  21. Chang, T.M.S., 1976c, Microencapsulation of enzymes and biologicals, in: “Methods in Enzymology: Immobilized Enzymes”, K. Mosbach, ed., Vol. XLIV, Academic Press, New York, pp. 201–217.Google Scholar
  22. Chang, T.M.S., 1976d, Biodegradable semipermeable microcapsules containing enzymes, hormones, vaccines and biologicals, J. Bioengineering. 1:25–32.Google Scholar
  23. Chang, T.M.S., 1976e, Methods for the therapeutic applications of immobilized enzymes, in: “Methods in Enzymology: Immobilized Enzymes”, K. Mosbach, ed., Vol. XLIV, Academic Press, New York, pp. 676–698.Google Scholar
  24. Chang, T.M.S., 1976f, Blood compatible microcapsules containing detoxicants, Canadian Patent, 982941.Google Scholar
  25. Chang, T.M.S., 1977a, Encapsulation of enzymes, cell contents, cells, vaccines, antigens, antiserums, cofactors, hormones, and proteins, in: “Biomedical Applications of Immobilized Enzymes and Proteins”, T.M.S. Chang, ed., Plenum Press, New York, Vol. 1, pp. 69–90.Google Scholar
  26. Chang, T.M.S., 1977b, Rationale and strategies for the therapeutic applications of immobilized enzymes, in: “Biomedical Applications of Immobilized Enzymes and Proteins”, T.M.S. Chang, ed., Plenum Press, New York, Vol. 1, pp. 93–104.Google Scholar
  27. Chang, T.M.S., ed., 1977d, “Biomedical Applications of Immobilized Enzymes and Proteins”, Plenum Press, New York, Vols. 1 & 2.Google Scholar
  28. Chang, T.M.S., ed., 1978, “Artificial Kidney, Artificial Liver, and Artificial Cells”, Plenum Press, New York.Google Scholar
  29. Chang, T.M.S., 1979a, Artificial cells as drug carriers in biology and medicine, in: “Drug Carriers in Biology and Medicine”, G. Gregoriadis, ed., Academic Press, New York, pp. 271–285.Google Scholar
  30. Chang, T.M.S., 1979b, Assessments of clinical trials of charcoal hemoperfusion in uremic patients, Clin. Nephrol., 11:111–119.PubMedGoogle Scholar
  31. Chang, T.M.S., 1980a, Clinical experience with ACAC coated charcoal hemoperfusion in acute intoxication, Clin. Toxicol., 17:429–542.Google Scholar
  32. Chang, T.M.S., 1980b, New approaches using immobilized enzymes for the removal of urea and ammonia, Enzyme Engineering. 5:225–229.Google Scholar
  33. Chang, T.M.S., 1980c, Artificial red blood cells, Trans. Amer. Soc. Artif. Intern. Organs, 26:354–357.Google Scholar
  34. Chang, T.M.S., 1981a, Current status of sorbent microencapsulation, in: “Advances in Basic and Clinical Nephrology”, Proc. 8th Intnl. Congress of Nephrology, S. Karger AG, Basel, pp. 400–406.Google Scholar
  35. Chang, T.M.S., ed., 1984, “Microencapsulation Including Artificial Cells”, Humana Press, New York.Google Scholar
  36. Chang, T.M.S., 1985a, Artificial cells with regenerating multienzyme systems, Methods in Enzymology, 112:195–203.PubMedGoogle Scholar
  37. Chang, T.M.S., 1985b, Biotechnology of artificial cells including its application in artificial organs. Chapter 6 in volume on “The principles, applications and regulations of biotechnology in Industry, Agriculture and Medicine” (CL COONEY, A HUMPHREY, eds.) in “Comprehensive Biotechnology:, Pergamon Press, New York. pp. 53–72.Google Scholar
  38. Chang, T.M.S., 1987a, Modified hemoglobin as red blood cell substitutes, J. Biomat. Art. Cells Art. Org., 15:323–328.Google Scholar
  39. Chang, T.M.S., 1987, Applications of Artificial Cells in Medicine and Biotechnology, Int. J. Biomaterials Artificial Cells and Artificial Organs. 15:1–20.Google Scholar
  40. Chang, T.M.S., 1987c, Recycling of NAD(P) by multienzyme systems immobilised by microencapsulation in artificial cells, Methods in Enzymology, 136:67–82.PubMedGoogle Scholar
  41. Chang, T.M.S., and R. Geyer (eds.), “Blood Substitutes”, Proceeding III International Symposium on Blood Substitutes, J. Biomat. Artif. Cells Art. Organs, Marcel Dekker Publisher, N.Y., 1988.Google Scholar
  42. Chang, T.M.S., and Wahl, E., 1986, Recycling of NAD cross-linked to albumin or hemoglobin immobilized with multienzyme systems in artificial cells, J of Molecular Catalysis. 39:147–154.Google Scholar
  43. Chang, T.M.S., and Gu, K.F., 1987, Conversion of ammonia or urea to L-leucine, L-valine and L-isoleucine by artificial cells, immobilized multienzyme system, Int. J. Biomaterials. Artificial Cells and Artificial Organs, 15:297–304.Google Scholar
  44. Chang, T.M.S., Farmer, M., Geyer, R.P., and Moss, G., 1987, Blood substitutes based on modified hemoglobin and fluorochemicals, TASAIO-Official Journal of Am. Soc. Artif. Int. Organs. 33.Google Scholar
  45. Chang, T.M.S., and Gu, K.F. (accepted), Conversion of ammonia or urea into L-leucine, L-valine and L-isoleucine using artificial cell immobilising multienzyme system and dextran-NADH+. I. Glucose dehydrogenase for cofactor recycling, TASAIO — Official Journal Am. Soc. Artif. Int. Organs.Google Scholar
  46. Chang, T.M.S., Coffey, J.F., Lister, C., Taroy, E., and Stark, A., 1973b, Methaqualone, methyprylon, and glutethimide clearance by the ACAC microcapsules artificial kidney: In vitro and in patients with acute intoxication, Trans. Amer. Soc. Artif. Intern. Organs. 19:87–91.Google Scholar
  47. Chang, T.M.S., Lister, G, Chirito, E., O’Keefe, P., and Resurreccion, E., 1978, Effects of hemoperfusion on the survival of fulminant hepatic failure rats, Trans. Amer. Soc. Artif. Intern. Organs, 24:243–245.Google Scholar
  48. Chang, T.M.S. and Loa, S.K., 1970, Urea removal by urease and ammonia adsorbent in the intestine, Physiologist, 13:70.Google Scholar
  49. Chang, T M.S., Macintosh, F.C., and Mason, S.G., 1966, Semipermeable aqueous microcapsules: I. Preparation and properties, Can. J. Physiol. Pharmacol., 44:115–128.Google Scholar
  50. Chang, T.M.S., Macintosh, F.C., and Mason, S.G., 1971, Encapsulated hydrophilic compositions and methods of making them, Canadian Patent, 873815.Google Scholar
  51. Chang, T.M.S. and Malouf, C., 1978, Artificial cells microencapsulated multienzyme system for converting urea and ammonia to amino acid using alpha-ketoglutarate and glucose as substrate, Trans. Amer. Soc. Artif. Intern. Organs. 24:18–20.Google Scholar
  52. Chang, T.M.S. and Malouf, C., 1979, Effects of glucose dehydrogenase in converting urea and ammonia into amino acid using artificial cells, Artif. Organs. 3(1):38–41.PubMedGoogle Scholar
  53. Chang, T.M.S., Malouf, C., and Resurreccion, E., 1979b, Artificial cells containing multienzyme systems for the sequential conversion of urea into ammonia, glutamate, then alanine, Artif. Organs, 3:S284–287.Google Scholar
  54. Chang, T.M.S. and Poznansky, M.J., 1968a, Semipermeable microcapsules containing catalse for enzyme replacement in acatalasemic mice, Nature, 218(5138):243–245.PubMedGoogle Scholar
  55. Chang, T.M.S. and Poznansky, M.J., 1968b, Semipermeable aqueous microcapsules (artificial cells): V. Permeability characteristics, J. Biomed. Mater. Res.. 2:187–199.PubMedGoogle Scholar
  56. Chang, T.M.S., Shu, C.D., Yu, Y.T., and Grunwald, J., 1982c, Artificial cells immobilized enzymes for metabolic disorders, in: “Advances in the Treatment of Inborn Errors of Metabolism”, M. Crawford, D. Gibbs and R. W. E. Watts, eds., John Wiley & Son Ltd., U.K., pp. 175–184.Google Scholar
  57. Chang, T.M.S., Yu, Y.T., and Grunwald, J., 1982d, Artificial cells immobilized multienzyme systems and cofactors, Enzyme Engineering, 6:451–561.Google Scholar
  58. Cousineau, J. and Chang, T.M.S., 1977, Formation of amino acid from urea and ammonia by sequential enzyme reaction using a microencapsulated multienzyme system, Biochem. Biophys. Res. Commun., 79(1):24–31.PubMedGoogle Scholar
  59. Damon Corporation, 1981, “Bulletin on Tissue Microencapsulation”, Needham Heights, MA.Google Scholar
  60. Djordjevich, L., Miller, I., 1980, Synthetic erythrocytes from lipid encapsulated hemoglobin, Exp. Hematol, 8:584.PubMedGoogle Scholar
  61. Gardner, D.L., Falb, R.D., Kim, B.C., and Emmerling, D.C., 1971, Possible uremic detoxification via oral-ingested microcapsules, Trans. Amer. Soc. Artif. Intern. Organs, 17:239.Google Scholar
  62. Gimson, A.E.S., Brande, S., Mellon, P.J., Canalese, J., and Williams, R., 1982, Earlier charcoal hemoperfusion in fulminant hepatic failure, Lancet, Sept:681–683.Google Scholar
  63. Grunwald, J. and Chang, T.M.S., 1978, Nylon polyethyleneimine microcapsules for immobilizing multienzymes with soluble dextran-NAD+ for the continuous recycling of the microencapsulated dextran-NAD+, Biochem. Biophys. Res. Commun., 81(2):565–570.PubMedGoogle Scholar
  64. Grunwald, J. and Chang, T.M.S., 1979, Continuous recycling of NAD+ using an immobilized system of collodion microcapsules containing dextran-NAD+, alcohol dehydrogenase, and malic dehydrogenase, J. Applied Biochem., 1:104–114.Google Scholar
  65. Grunwald, J. and Chang, T.M.S., 1981, Immobilization of alcohol dehydrogenase, malic dehydrogenase and dextran-NAD+ within nylon-polyethyleneimine microcapsules: Preparation and cofactor recycling, J. Molecular Catalysis. 11:83–90.Google Scholar
  66. Gu, K.F. and Chang, T.M.S., 1987, Conversion of ammonia or urea to L-leucine, L-valine and L-isoleucine by Artificial Cells,immobilized multienzyme system, Int. J. Biomaterials. Artificial Cells and Artificial Organs, 1987.Google Scholar
  67. Hunt, A.C., Burnette, R.R., 1983, Neohemocytes, in: Advances in Blood Substitute Research”, R. B. Bolin, R. P. Geyer, and G. J. Nemo, eds., Alan R. Liss Inc., New York, pp. 59–70.Google Scholar
  68. Ihler, G.M., Glew, R.H., and Schnure, F. W., 1973, Enzyme loading of erythrocytes, Proc. Natl. Acad. Sci. U.S.. 70:2663.Google Scholar
  69. Ilan, E., and Chang, T.M.S., 1986, Modification of lipid-polyamide microcapsules for immobilization of free cofactors and multienyzme system for the conversion of ammonia to glutamate, Applied Biochemistry and Biotechnology, 13:221–230.PubMedGoogle Scholar
  70. Jamieson, G.A. and Greenwalt, T.J., 1978, “Blood Substitutes and Plasma Expanders”, Alan R. Liss, Inc., New York.Google Scholar
  71. Keipert, P.E., Minkowitz, J., and Chang, T.M.S., 1982, Cross-linked stroma-free polyhemoglobin as a potential blood substitute. Intl. J. Artif. Organs, 5:383–385.Google Scholar
  72. Keipert, P.E. and Chang, T.M.S., 1983, In vivo assessment of pyridoxylated cross-linked polyhemoglobin as artificial red blood cells, Trans. Amer. Soc. Artif. Intern. Organs, 29:329–33.Google Scholar
  73. Keipert, P.E. and Chang, T.M.S., 1985, Pyridoxylated polyhemoglobin as a blood substitute for resuscitation of lethal hemorrhagic shock in conscious rats, Biomat. Med. Dev., Artif. Organs, 13:1–15.Google Scholar
  74. Kitajima, M. and Kondo, A., 1971, Fermentation with multiplication of cells using microcapsules that contain zymase complex and muscle enzyme extract, Bull. Chem. Soc. Japan, 44:3201.Google Scholar
  75. Kjellstrand, C., Borges, H., Pru, C., Gardner, D., and Fink, D., 1981, Urease-zirconium-phosphate microcapsules (UZP) effectively decreases nitrogen accumulation in CRF patients, Trans. Amer. Soc. Artif. Intern. Organs. 27:24–30.Google Scholar
  76. Lim, F. and Sun, A.M., 1980, Microencapsulated islets as bioartificial endocrine pancreas, Science, 210:908.PubMedGoogle Scholar
  77. May, S.W. and Li, N.N., 1972, The immobilization of urease using liquid- surfactant membranes, Biochem. Biophys. Res. Commun., 47:1179.PubMedGoogle Scholar
  78. Mori, T., Tosa, T., and Chibata, I., 1973, Enzymatic properties of micro-capsules containing asparaginase, Biochim. Biophys. Acta, 321:653.PubMedGoogle Scholar
  79. Mosbach, K. and Mosbach, R., 1966, Entrapment of enzymes and micro-organisms in synthetic cross-linked polymers and their applications in volume techniques, Acta Chem. Scan., 20:2807.Google Scholar
  80. Mueller, P. and Rudin, D.O., 1968, Resting and action potentials in experimental lipid membranes, J. Theoret. Biol., 18:222.Google Scholar
  81. Ostergaard, J.C.W. and Martiny, S.C., 1973, Immobilization of beta- galactosidase through encapsulation in water insoluble microcapsules, Biotechnol. Bioeng., 15:561.PubMedGoogle Scholar
  82. Poznansky, M. and Chang, T.M.S., 1974, Comparison of the enzyme kinetics and immunological properties of catalase immobilized by microencapsulation and catalase in free solution for enzyme replacement, Biochim. Biophys. Acta, 334:103.Google Scholar
  83. Rosenthal, A.M. and Chang, T.M.S., 1980, The incorporation of lipid and Na+-K+-ATPase into the membranes of semipermeable microcapsules, J. Membrane Science, 6(3):329–338.Google Scholar
  84. Sekiguchi, W. and Kondo, A., 1966, Studies of microencapsulated hemoglobin, J. Japan Soc. Blood Transfusion, 13:153–154.Google Scholar
  85. Sessa, G. and Weissman, G., 1970, Incorporation of lysozyme into liposomes, J. Biol. Chem., 245:3295.PubMedGoogle Scholar
  86. Shiba, M., Tomioka, S., Koishi, M., and Kondo, T., 1970, Studies on microcapsules: V. Preparation of polyamide microcapsules containing aqueous protein solution, Chem. Pharm. Bull. (Tokyo), 18:803.Google Scholar
  87. Shu, C.D. and Chang, T.M.S., 1980, Tyrosinase immobilized with artificial cells for detoxification in liver failure. I. Preparation and in-vitro studies, Intl. J. Artif. Organs, 3(5):287–291.Google Scholar
  88. Shu, C.D. and Chang, T.M.S., 1981, Tyrosinase immobilized within artificial cells for detoxification in liver failure: II. In-vivo studies in fulminant hepatic failure rats, Intl. J. Artif. Organs, 4:82–84.Google Scholar
  89. Siu Chong, E.D. and Chang, T.M.S., 1974, In-vivo effects of intra-peritoneally injected L-asparaginase solution and L-asparaginase immobilized within semipermeable nylon microcapsules with emphasis on blood L-asparaginase, ‘body’ L-asparaginase, and plasma L-asparagine levels, Enzyme, 18:218–239.PubMedGoogle Scholar
  90. Sparks, R.E., Mason, N.S., Samuels, W.E., Litt, M.H. and Lindan, O., 1972, Binders to remove uremic waste metabolites from the GI tract, Trans. Amer. Soc. Artif. Intern. Organs, 18:458–464.Google Scholar
  91. Tabata, Y. and Chang, T.M.S., 1980, Comparisons of six artificial live support regimes in fulminant hepatic coma rats, Trans. Amer. Soc. Artif. Intern. Organs, 26:394–399.Google Scholar
  92. Williams, R. and Murray-Lyon, I.M., eds., 1975, “Artificial Liver Support”, Pitman Press, London.Google Scholar
  93. Wong, H. and Chang T.M.S., 1986, Bioartificial liver: implanted artificial cells microencapsulated living hepatocytes increases survival of liver failure rats, Int. J. Artif. Organs, 9:335–336.PubMedGoogle Scholar
  94. Yu, Y.T. and Chang, T.M.S., 1981a, Ultrathin lipid-polymer membrane microcapsules containing multienzymes, cofactors and substrates for multistep enzyme reactions, FEBS Letters. 125(1):94–96.PubMedGoogle Scholar
  95. Yu, Y.T. and Chang, T.M.S., 1981b, Lipid-polymer membrane artificial cells containing multienzyme systems, cofactors and substrates for the removal of ammonia and urea, Trans. Amer. Soc. Artif. Intern. Organs, 27:535–538.Google Scholar
  96. Yu, Y.T. and Chang, T.M.S., 1982, Lipid-polyamide membrane microcapsules immobilized multienzymes and cofactors for sequential conversion of lipophilic and lipophobic substrates, J. Microbial & Enzyme Technol., 4:327–331.Google Scholar
  97. Zhou, M.X. and Chang T.M.S., 1987, Effects of polyactic acid containing prostaglandin E2 on the survival rates of grade II coma galactosamine-induced fulminant hepatic failure rats, J. Biomat. Art. Cells Art. Org., 15:549–558.Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • T. M. S. Chang
    • 1
  1. 1.Artificial Cells and Organs Research Centre Faculty of MedicineMcGill UniversityMontrealCanada

Personalised recommendations