Parsa Zamankhan

Epithelium damage and protection during reopening of occluded airways in a physiologic microfluidic pulmonary airway model

Airways of the peripheral lung are prone to closure at low lung volumes. Deficiency or dysfunction of pulmonary surfactant during various lung diseases compounds this event by destabilizing the liquid lining of small airways and giving rise to occluding liquid plugs in airways. Propagation of liquid plugs in airways during inflation of the lung exerts large mechanical forces on airway cells. We describe a microfluidic model of small airways of the lung that mimics airway architecture, recreates physiologic levels of pulmonary pressures, and allows studying cellular response to repeated liquid plug propagation events. Substantial cellular injury happens due to the propagation of liquid plugs devoid of surfactant. We show that addition of a physiologic concentration of a clinical surfactant, Survanta, to propagating liquid plugs protects the epithelium and significantly reduces cell death. Although the protective role of surfactants has been demonstrated in models of a propagating air finger in liquid-filled airways, this is the first time to study the protective role of surfactants in liquid plugs where fluid mechanical stresses are expected to be higher than in air fingers. Our parallel computational simulations revealed a significant decrease in mechanical forces in the presence of surfactant, confirming the experimental observations. The results support the practice of providing exogenous surfactant to patients in certain clinical settings as a protective mechanism against pathologic flows. More importantly, this platform provides a useful model to investigate various surface tension-mediated lung diseases at the cellular level.

Microprinted feeder cells guide embryonic stem cell fate.

We introduce a non-contact approach to microprint multiple types of feeder cells in a microarray format using immiscible aqueous solutions of two biopolymers. Droplets of cell suspension in the denser aqueous phase are printed on a substrate residing within a bath of the immersion aqueous phase. Due to their affinity to the denser phase, cells remain localized within the drops and adhere to regions of the substrate underneath the drops. We show the utility of this technology for creating duplex heterocellular stem cell niches by printing two different support cell types on a gel surface and overlaying them with mouse embryonic stem cells (mESCs). As desired, the type of printed support cell spatially direct the fate of overlaid mESCs. Interestingly, we found that interspaced mESCs colonies on differentiation-inducing feeder cells show enhanced neuronal differentiation and give rise to dense networks of neurons. This cell printing technology provides unprecedented capabilities to efficiently identify the role of various feeder cells in guiding the fate of stem cells.

Transient motion of liquid plugs with yield stress in human airways

The airway closure due to capillary instability [1] occurs in lung diseases such as asthma, cystic fibrosis, or emphysema. The reopening process involves displacement of plugs constituted from mucus, a non-Newtonian fluid with a yield stress, in the airways. In this work the transient propagation of mucus plugs in a 2D channel is studied numerically, assuming that the mucus is a Bingham fluid. The governing equations are discretized by a spectral element formulation and the free surface is resolved with an Arbitrary Lagrangian Eulerian (ALE) approach [2]. The constitutive equation for a Bingham fluid is implemented through a regularized constitutive equation. According to the numerical results, the yield stress behavior of the plug modifies the plug shape, the pattern of the streamlines and the distribution of stresses in the plug domain and along the walls in a significant way. The distribution along the walls is a major factor in studying cell injuries.Copyright

Propagation of liquid plugs with yield stress in human airways

The airway closure due to the capillary instability [1] occurs in lung diseases such as asthma, cystic fibrosis, or emphysema. The reopening process involves with displacement of plugs constituted from mucus, a non-Newtonian fluid with a yield stress, in the airways. In this work the steady propagation of mucus plugs in a 2D channel is studied numerically, assuming that the mucus is a Bingham fluid. The governing equations are solved by a mixed-discontinuous finite element formulation and the free surface is resolved with the method of spines. The constitutive equation for Bingham fluid is implemented through a regularized constitutive equation. According to the numerical results, the yield stress behavior of the plug modifies the plug shape, the pattern of the streamlines and the distribution of stresses in the plug domain and along the walls in a significant way. The distribution along the walls is a major factor in studying cell injuries.Copyright

Steady state creeping displacement of a semi-infinite gas bubble in a 2D channel filled by a bingham liquid

The mucus layer which covers the respiratory tract is a non-Newtonian fluid with a yield stress. The amount of shear stress must exceed a certain value before significant deformation (i.e. flow) can occur. Therefore, for better understanding of some interesting phenomena in the airways, such as the propagation or rupture of a mucus plug, as may occur in asthma, cystic fibrosis, or emphysema, the yield stress behavior of the fluid needs to be considered as well.© 2009 ASME