Biomimetic in Silico Devices

  • C. Anthony Hunt
  • Glen E. P. Ropella
  • Michael S. Roberts
  • Li Yan
Part of the Lecture Notes in Computer Science book series (LNCS, volume 3082)


We introduce biomimetic in silico devices, and means for validation along with methods for testing and refining them. The devices are constructed from adaptable software components designed to map logically to biological components at multiple levels of resolution. In this report we focus on the liver; the goal is to validate components that mimic features of the lobule (the hepatic primary functional unit) and dynamic aspects of liver behavior, structure, and function. An assembly of lobule-mimetic devices represents an in silico liver. We validate against outflow profiles for sucrose administered as a bolus to isolated, perfused rat livers. Acceptable in silico profiles are experimentally indistinguishable from those of the in situ referent. This new technology is intended to provide powerful new tools for challenging our understanding of how biological functional units function in vivo.


Central Hepatic Vein Bile Canaliculus Secondary Unit Solute Object Outflow Profile 
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. 1.
    Roberts, M., Magnusson, B., Burczynski, F., Weiss, M.: Enterohepatic Circulation: Physiological, Pharmacokinetic and Clinical Implications. Clin. Pharmacokinet 41, 751–790 (2002)CrossRefGoogle Scholar
  2. 2.
    Noble, D.: The Rise of Computational Biology. Nat. Rev. Mol. Cell. Bio. 3, 460–463 (2002)CrossRefGoogle Scholar
  3. 3.
    Noble, D.: The Future: Putting Humpty-Dumpty Together Again. Biochem. Soc. Transact. 31, 156–158 (2003)CrossRefGoogle Scholar
  4. 4.
    Roberts, M.S., Anissimov, Y.G.: Modeling of Hepatic Elimination and Organ Distribution Kinetics with the Extended Convection-Dispersion Model. J. Pharmacokin. Biopharm. 27, 343–382 (1999)CrossRefGoogle Scholar
  5. 5.
    Hung, D.Y., Chang, P., Weiss, M., Roberts, M.S.: Structure-Hepatic Disposition Relationships for Cationic Drugs in Isolated Perfused Rat Livers: Transmembrane Exchange and Cytoplasmic Binding Process. J. Pharmacol. Exper. Therap. 297, 780–789 (2001)Google Scholar
  6. 6.
    Falkenhainer, B., Forbus, K.D.: Compositional Modeling: Finding the Right Model for the Job. Art. Intel. 51, 95–143 (1991)CrossRefGoogle Scholar
  7. 7.
    Santini, S., Jain, R.: Similarity Measures. IEEE Tran. Pattern Analysis and Machine Intelligence 21, 871–883 (1999)CrossRefGoogle Scholar
  8. 8.
    Teutsch, H.F., Schuerfeld, D., Groezinger, E.: Three-Dimensional Reconstruction of Parenchymal Units in the Liver of the Rat. Hepatology 29, 494–505 (1999)CrossRefGoogle Scholar
  9. 9.
    Burns, A., Davies, G.: Concurrent Programming, pp. 1–2. Addison-Wesley, Reading (1993)zbMATHGoogle Scholar
  10. 10.
    Sanchez, S.M., Lucas, T.W.: Exploring the World of Agent-Based Simulations: Simple Models, Complex Analyses. In: Yücesan, E., Chen, C.-H., Snowdon, J.L., Charnes, C.M. (eds.) Proceedings of the 2002 Winter Simulation Conference, pp. 116–126 (2002)Google Scholar
  11. 11.
    Gumucio, J.J., Miller, D.L.: Zonal Hepatic Function: Solute-Hepatocyte Interactions Within the Liver Acinus. Prog. Liver Diseases 7, 17–30 (1982)Google Scholar
  12. 12.
    Tyson, J.J., Chen, K., Novak, B.: Network Dynamics and Cell Physiology. Nat. Revs. Mol. Cell Biol. 2, 908–917 (2001)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • C. Anthony Hunt
    • 1
    • 3
  • Glen E. P. Ropella
    • 1
  • Michael S. Roberts
    • 2
  • Li Yan
    • 3
  1. 1.Dept. of Biopharmaceutical Sciences, Biosystems GroupUniversity of CaliforniaSan FranciscoUSA
  2. 2.Department of MedicineUniversity of Queensland, Princess Alexandra HospitalWoolloongabbaAustralia
  3. 3.Joint UCSF/UC Berkeley Bioengineering Graduate ProgramUSA

Personalised recommendations