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Quantitative and Temporal Control of Oxygen Microenvironment at the Single Islet Level
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Hypoxic behavior in cells under controlled microfluidic environment.

Adnan Morshed1, Prashanta Dutta1

  • 1School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164-2920, United States.

Biochimica Et Biophysica Acta. General Subjects
|January 24, 2017
PubMed
Summary
This summary is machine-generated.

This study models cellular responses to low oxygen (hypoxia) using a microfluidic system. The findings reveal how oxygen levels and nutrients like ascorbate influence hypoxia-inducible factors (HIF) hydroxylation, crucial for cellular metabolism.

Keywords:
HIFHypoxic responseascorbatecomputational biologymicrofluidics

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Area of Science:

  • Biomedical Engineering
  • Cellular Biology
  • Mathematical Modeling

Background:

  • Hypoxia, or depleted oxygen, significantly alters cellular metabolism.
  • Hypoxia-inducible factors (HIF) are key regulators of cellular responses to hypoxia.
  • Intracellular responses to hypoxia are highly dependent on the extracellular microenvironment.

Purpose of the Study:

  • To develop and analyze a detailed model of a hypoxic cellular microenvironment in a microfluidic setting.
  • To investigate the role of HIF hydroxylation within this model.
  • To explore the influence of extracellular factors on intracellular responses to hypoxia.

Main Methods:

  • Modeled hypoxia induction in a microfluidic chip via oxygen permeation through a porous wall.
  • Employed two distinct mathematical descriptions for extracellular and intracellular interactions.
  • Coupled intracellular space to the extracellular environment, accounting for oxygen and ascorbate uptake and consumption.

Main Results:

  • Observed a distinct shift in HIF hydroxylation behavior with varying prolyl hydroxylase levels (0.1-4.0μM).
  • Modeled extracellular ascorbate concentration to predict intracellular accumulation within a physiological range.
  • Demonstrated significant dependence of intracellular responses on oxygen levels under varying hypoxic conditions.

Conclusions:

  • Changes in HIF hydroxylation and nutrient availability offer potential for new cancer and ischemia/reperfusion therapies.
  • The hybrid mathematical model accurately predicts intracellular behavior influenced by external factors.
  • Provides valuable insights for designing future experimental studies on cellular responses to hypoxia.