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Related Experiment Videos

Modeling tight junction dynamics and oscillations.

Fuad Kassab1, Ricardo Paulino Marques, Francisco Lacaz-Vieira

  • 1Escola Politécnica, Departamento de Engenharia de Telecomunicaçoes e Controle. Departmento de Fisiologia e Biofísica, Instituto de Ciencias Biomédicas, Universidade de São Paulo, 05508-900 São Paulo, Brazil.

The Journal of General Physiology
|August 1, 2002
PubMed
Summary

Tight junction (TJ) permeability is regulated by a feedback control loop involving calcium. Mathematical modeling accurately predicts TJ dynamics and oscillations observed in frog urinary bladders.

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Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference·2007
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Area of Science:

  • Cell Biology
  • Biophysics
  • Physiology

Background:

  • Tight junctions (TJs) control paracellular transport and their permeability is sensitive to extracellular calcium (Ca(2+)).
  • Transepithelial electrical conductance (G) in the absence of Na(+) serves as a measure of TJ permeability.
  • The fast Ca(2+) switch assay (FCSA) is used to study early events in TJ dynamics.

Purpose of the Study:

  • To evaluate the early events of TJ dynamics using the FCSA.
  • To investigate the feedback control loop regulating TJ permeability in response to calcium.
  • To develop a mathematical model explaining TJ dynamics and observed oscillations.

Main Methods:

  • Utilized the fast Ca(2+) switch assay (FCSA) to manipulate basal calcium (Ca(2+)(bl)) and observe TJ responses.

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  • Developed a mathematical model simulating calcium diffusion and TJ barrier regulation.
  • Applied Fick's laws of diffusion to model Ca(2+) movement in the extracellular route and across TJs.

    • Main Results:

    • Observed oscillations in TJ permeability when basal calcium was removed in the presence of apical calcium (Ca(2+)(ap)).
    • The developed mathematical model successfully simulated experimental results, including TJ opening/closing, steady-state attainment, escape phases, and Ca(2+)(ap)-dependent oscillation frequencies.
    • The model supports a feedback control loop involving Ca(2+) sensor sites, a cellular control unit, and TJs as effectors.

    Conclusions:

    • TJ permeability is dynamically regulated by a feedback control loop sensitive to extracellular calcium concentrations.
    • The mathematical model provides a robust framework for understanding TJ behavior and calcium-mediated regulation.
    • The findings offer insights into the biophysical mechanisms governing paracellular transport and epithelial barrier function.