Hypoxic behavior in cells under controlled microfluidic environment

Adnan Morshed; Prashanta Dutta

doi:10.1016/j.bbagen.2017.01.017

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Hypoxic behavior in cells under controlled microfluidic environment

Journal article

Open access

Peer reviewed

Hypoxic behavior in cells under controlled microfluidic environment

Adnan Morshed and Prashanta Dutta

Biochimica et biophysica acta. General subjects, Vol.1861(4), pp.759-771

04/2017

DOI: https://doi.org/10.1016/j.bbagen.2017.01.017

Handle:

https://hdl.handle.net/2376/101511

PMID: 28111315

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Abstract

Models, Theoretical

Neoplasms - metabolism

Cell Hypoxia - physiology

Reperfusion Injury - pathology

Humans

Hydroxylation - physiology

Hypoxia-Inducible Factor 1 - metabolism

Oxygen - metabolism

Models, Biological

Cellular Microenvironment - physiology

Neoplasms - pathology

Microfluidics - methods

Reperfusion Injury - metabolism

Depleted oxygen levels, known as hypoxia, causes considerable changes in the cellular metabolism. Hypoxia-inducible factors (HIF) act as the major protagonist in orchestrating manifold hypoxic responses by escaping cellular degradation mechanisms. These complex and dynamic intracellular responses are significantly dependent on the extracellular environment. In this study, we present a detailed model of a hypoxic cellular microenvironment in a microfluidic setting involving HIF hydroxylation. We have modeled the induction of hypoxia in a microfluidic chip by an unsteady permeation of oxygen from the microchannel through a porous polydimethylsiloxane channel wall. Extracellular and intracellular interactions were modeled with two different mathematical descriptions. Intracellular space is directly coupled to the extracellular environment through uptake and consumption of oxygen and ascorbate similar to cells in vivo. Our results indicate a sharp switch in HIF hydroxylation behavior with changing prolyl hydroxylase levels from 0.1 to 4.0μM. Furthermore, we studied the effects of extracellular ascorbate concentration, using a new model, to predict its accumulation inside the cell over a relevant physiological range. In different hypoxic conditions, the cellular environment showed a significant dependence on oxygen levels in resulting intracellular response. Change in hydroxylation behavior and nutrient supplementation can have significant potential in designing novel therapeutic interventions in cancer and ischemia/reperfusion injuries. The hybrid mathematical model can effectively predict intracellular behavior due to external influences providing valuable directions in designing future experiments.

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Title: Hypoxic behavior in cells under controlled microfluidic environment
Creators: Adnan Morshed - School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164-2920, United States
Prashanta Dutta - School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164-2920, United States. Electronic address: prashanta@wsu.edu
Publication Details: Biochimica et biophysica acta. General subjects, Vol.1861(4), pp.759-771
Academic Unit: Mechanical and Materials Engineering, School of
Publisher: Netherlands
Identifiers: 99900546643101842
Language: English
Resource Type: Journal article