Determining Cell Fate Transition Probabilities to VEGF/Ang 1 Levels: Relating Computational Modeling to Microfluidic Angiogenesis Studies

Abstract

Angiogenesis is crucial during many physiological processes, and is influenced by various biochemical and biomechanical factors. Two such factors: VEGF and Ang 1 are known to be critical and we demonstrate here their effect of sprout formation in an in vitro microfluidic system. Previously, we have developed a 3D hybrid, agent-field model where individual cells are modeled as sprout-forming agents in a matrix field. We have conducted microfluidic experiments under different concentrations of VEGF and Ang 1 and analyzed the difference in sprout number and sprout lengths using Decision Tree Analysis. We demonstrate that under specific transition probabilities, the model gives us capillary characteristics similar to those seen in experiments (R 2 ~ 0.82–0.99). Thus, this model can be used to cluster sprout morphology as a function of various influencing factors and, within bounds, predict if a certain growth factor will affect migration or proliferation as it impacts sprout morphology

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Acknowledgments

We would like to thank Wahleed Farhat for designing the microfluidic device wafers. We would like to acknowledge NSF-EFRI grant# 0735997 and the Singapore-MIT Alliance for Research and Technology for funding.

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Correspondence to Anusuya Das.

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Associate Editor David Odde oversaw the review of this article.

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Well developed sprouts were observed under conditions with relatively high concentration of Ang 1. The sprouts obtained were tubular with fewer active cells (Fig. 1). Poorly developed sprouts were obtained when the vEGF concentrations were high, but Ang 1 concentrations were low. They were not tubular and had many active cells along the sprouts. (Fig. 2)

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Das, A., Lauffenburger, D., Asada, H. et al. Determining Cell Fate Transition Probabilities to VEGF/Ang 1 Levels: Relating Computational Modeling to Microfluidic Angiogenesis Studies. Cel. Mol. Bioeng. 3, 345–360 (2010). https://doi.org/10.1007/s12195-010-0146-7

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Keywords

  • Angiogenesis
  • Capillary characteristics
  • Microfluidics