Rapid tumor growth can result in
localized zones in the tumor microenvironment where cells
have far less access to nutrients. The scarcity of
nutrients such as oxygen and ascorbate plays a critical
role in the fate of tumor microenvironment. For example,
hypoxia, the depletion of intracellular oxygen levels
below 6\%, initiates major changes in cellular dynamics
causing tumor cell survival by escaping cellular
degradation mechanisms. The intercapillary distance
(distance between adjacent blood vessels) across a colony
of growing tumor cells and the flow around the colony are
believed to be important factors for the initiation of
hypoxia. Although cellular dynamics have been studied
extensively for a specific hypoxia, all these models
consider only the intracellular dynamics and for the most
part, treat the species inside as a well-mixed system.
However, it is well established that cellular uptake and
consumption of nutrients like oxygen, ascorbate and iron
from the extracellular environment are continuous
processes, which cannot be properly represented only with
an intracellular model. In this talk, we will present a
hybrid model to study the transport and evolution of
different species in both extracellular and intracellular
spaces of a hypoxic cellular microenvironment in a
microfluidic setting. We will discuss the effect of
different key parameters, such as flow strength, the
spatial distribution of nutrients, effective diffusion
coefficients, and the intercapillary distance on the
dynamics of intracellular species inside a colony of tumor
cells. We will also discuss how a change in hydroxylation
behavior and nutrient supplementation can potentially help
us in designing novel therapeutic interventions for
cancer.
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