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Towards integration of time-resolved confocal microscopy of a 3D in vitro microfluidic platform with a hybrid multiscale model of tumor angiogenesis

Phillips, Caleb M ; Lima, Ernesto A B F ; Gadde, Manasa ; Jarrett, Angela M ; Rylander, Marissa Nichole ; Yankeelov, Thomas E Maini, Philip K.

PLoS computational biology, 2023-01, Vol.19 (1), p.e1009499-e1009499 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Towards integration of time-resolved confocal microscopy of a 3D in vitro microfluidic platform with a hybrid multiscale model of tumor angiogenesis
Autor: Phillips, Caleb M ; Lima, Ernesto A B F ; Gadde, Manasa ; Jarrett, Angela M ; Rylander, Marissa Nichole ; Yankeelov, Thomas E
Maini, Philip K.
Assuntos: Angiogenesis ; Biology and Life Sciences ; Blood vessels ; Breast cancer ; Calibration ; Cell growth ; Collagen ; Confocal microscopy ; Continuum modeling ; Density ; Development and progression ; Differential equations ; Endothelial cells ; Engineering and Technology ; Growth factors ; Health aspects ; Humans ; Inflammation ; Mathematical models ; Medical research ; Medicine and Health Sciences ; Methods ; Microfluidics ; Microscopy ; Microscopy, Confocal ; Morphology ; Neovascularization ; Neovascularization, Pathologic - pathology ; Neovascularization, Physiologic ; Observations ; Ordinary differential equations ; Parameters ; Predictions ; Research and Analysis Methods ; Scale models ; Spatial distribution ; Temporal distribution ; Tumor cells ; Tumors ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - metabolism ; Vascular Endothelial Growth Factors
É parte de: PLoS computational biology, 2023-01, Vol.19 (1), p.e1009499-e1009499
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The authors have declared that no competing interests exist.
Descrição: The goal of this study is to calibrate a multiscale model of tumor angiogenesis with time-resolved data to allow for systematic testing of mathematical predictions of vascular sprouting. The multi-scale model consists of an agent-based description of tumor and endothelial cell dynamics coupled to a continuum model of vascular endothelial growth factor concentration. First, we calibrate ordinary differential equation models to time-resolved protein concentration data to estimate the rates of secretion and consumption of vascular endothelial growth factor by endothelial and tumor cells, respectively. These parameters are then input into the multiscale tumor angiogenesis model, and the remaining model parameters are then calibrated to time resolved confocal microscopy images obtained within a 3D vascularized microfluidic platform. The microfluidic platform mimics a functional blood vessel with a surrounding collagen matrix seeded with inflammatory breast cancer cells, which induce tumor angiogenesis. Once the multi-scale model is fully parameterized, we forecast the spatiotemporal distribution of vascular sprouts at future time points and directly compare the predictions to experimentally measured data. We assess the ability of our model to globally recapitulate angiogenic vasculature density, resulting in an average relative calibration error of 17.7% ± 6.3% and an average prediction error of 20.2% ± 4% and 21.7% ± 3.6% using one and four calibrated parameters, respectively. We then assess the model's ability to predict local vessel morphology (individualized vessel structure as opposed to global vascular density), initialized with the first time point and calibrated with two intermediate time points. In this study, we have rigorously calibrated a mechanism-based, multiscale, mathematical model of angiogenic sprouting to multimodal experimental data to make specific, testable predictions.
Editor: United States: Public Library of Science
Idioma: Inglês

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Towards integration of time-resolved confocal microscopy of a 3D in vitro microfluidic platform with a hybrid multiscale model of tumor angiogenesis

Phillips, Caleb M ; Lima, Ernesto A B F ; Gadde, Manasa ; Jarrett, Angela M ; Rylander, Marissa Nichole ; Yankeelov, Thomas E Maini, Philip K.

United States: Public Library of Science

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