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Computational studies of particles and cells transport in microfluidic devices

University of British Columbia

Bio-mimicking microfluidic devices have been developed to provide a biologically relevant framework for drug development and toxicological studies. This dissertation aims to describe three case studies in the area of particle and cell transport in bio-mimicking microfluidic devices using finite-element simulations. In the first study, we model the deposition of submicron particles on the epithelial layer of a well-established lung-on-a-chip device. As main results of the study, our simulations predict enhanced submicron particle deposition during physical exercising, subject to opposing effects of elevated air volume and breathing frequency. Moreover, the deposition efficiency varies non-monotonically with particle size, due to the distinct effects of gravitational settling and Brownian motion. In the second case study, we propose a biomechanical model for the passage of a tumor cell through the endothelial cells monolayer. Based on prior in vitro observations, we assume that the tumor cell extends a protrusion between adjacent endothelial cells that adheres to the extracellular matrix. Inside the protrusion, a contractile element composed of stress-fibers and focal-adhesions pulls the nucleus through the endothelial opening. We modeled the chemo-mechanics of the contractile element as well as the elastic deformation and cytosolic flow during transmigration process. Using physiologically reasonable parameters, our model shows that the contractile element can produce a force on the order of 70 nN, which is sufficient to deform the endothelial cells for transmigration. The third project deals with the tenertaxis hypothesis. During immune reaction, leukocytes transmigrate either directly through the body of an individual endothelial cell (the transcellular route) or from the junction between adjacent endothelial cells (the paracellular route). What determines the usage of one route over the other is ambiguous. A recently proposed tenertaxis hypothesis claims that leukocytes choose the path with less mechanical resistance against leukocyte protrusions. Our simulations results show that the required force to breach the endothelium through the transcellular route is greater than paracellular route (22 pN versus 15 pN). Moreover, experiments have demonstrated that manipulation of the relative strength of endothelial resistance can make the transcellular route preferable. Our simulations have confirmed this reversal, and thus tentatively confirmed the hypothesis of tenertaxis.

Text

2021-03-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/77683

Chemical and Biological Engineering

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/