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Morphogenetic Implications of Peristalsis-Driven Fluid Flow in the Embryonic Lung.

Bokka KK, Jesudason EC, Lozoya OA, Guilak F, Warburton D, Lubkin SR - PLoS ONE (2015)

Bottom Line: The sensation of internal fluid flows has been shown to have potent morphogenetic effects, as has the transport of morphogens.We hypothesize that these effects play an important role in lung morphogenesis.We analyzed the interaction between the internal flows and diffusion and conclude that AP has a strong effect on flow sensing away from the tip and on transport of morphogens.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical Engineering, North Carolina State University, Raleigh, North Carolina, United States of America.

ABSTRACT
Epithelial organs are almost universally secretory. The lung secretes mucus of extremely variable consistency. In the early prenatal period, the secretions are of largely unknown composition, consistency, and flow rates. In addition to net outflow from secretion, the embryonic lung exhibits transient reversing flows from peristalsis. Airway peristalsis (AP) begins as soon as the smooth muscle forms, and persists until birth. Since the prenatal lung is liquid-filled, smooth muscle action can transport fluid far from the immediately adjacent tissues. The sensation of internal fluid flows has been shown to have potent morphogenetic effects, as has the transport of morphogens. We hypothesize that these effects play an important role in lung morphogenesis. To test these hypotheses in a quantitative framework, we analyzed the fluid-structure interactions between embryonic tissues and lumen fluid resulting from peristaltic waves that partially occlude the airway. We found that if the airway is closed, fluid transport is minimal; by contrast, if the trachea is open, shear rates can be very high, particularly at the stenosis. We performed a parametric analysis of flow characteristics' dependence on tissue stiffnesses, smooth muscle force, geometry, and fluid viscosity, and found that most of these relationships are governed by simple ratios. We measured the viscosity of prenatal lung fluid with passive bead microrheology. This paper reports the first measurements of the viscosity of embryonic lung lumen fluid. In the range tested, lumen fluid can be considered Newtonian, with a viscosity of 0.016 ± 0.008 Pa-s. We analyzed the interaction between the internal flows and diffusion and conclude that AP has a strong effect on flow sensing away from the tip and on transport of morphogens. These effects may be the intermediate mechanisms for the enhancement of branching seen in occluded embryonic lungs.

No MeSH data available.


Related in: MedlinePlus

Time scales of transport in the embryonic lung.In the absence of flow, solutes can only diffuse (dotted curve). In the absence of diffusion, solutes and particles advect with the flow (dashed curve). Advection-diffusion (solid curve) transports solutes rapidly relative to diffusion alone, and a small occlusion from weak airway peristalsis can yield a dramatic reduction in transport time. 100 kDa globular protein in lumen fluid of measured viscosity 0.016 Pa-s.
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pone.0132015.g007: Time scales of transport in the embryonic lung.In the absence of flow, solutes can only diffuse (dotted curve). In the absence of diffusion, solutes and particles advect with the flow (dashed curve). Advection-diffusion (solid curve) transports solutes rapidly relative to diffusion alone, and a small occlusion from weak airway peristalsis can yield a dramatic reduction in transport time. 100 kDa globular protein in lumen fluid of measured viscosity 0.016 Pa-s.

Mentions: When AP begins, it is weak, and occlusions are small. The reflux velocity will be correspondingly smaller, and advection and diffusion interact in the intermediate range of Taylor dispersion [15, 16]. In this regime, solutes diffuse with an effective diffusion coefficient , where a is the lumen radius, bounded by the molecular diffusion coefficient D, giving (Fig 7). For example, for a 100 kDa globular protein in the embryonic lung lumen with viscosity 0.016 Pa-s and tubule inner radius 25 μm, the time scale to diffuse 100 μm is 30 minutes, but 1 mm takes 2 days. With a peristaltic wave at 50 μm/s and just 10% occlusion, yielding μm/s, that 100 kDa protein is transported 1 mm in an hour instead of 2 days, because of the interaction between advection and diffusion.


Morphogenetic Implications of Peristalsis-Driven Fluid Flow in the Embryonic Lung.

Bokka KK, Jesudason EC, Lozoya OA, Guilak F, Warburton D, Lubkin SR - PLoS ONE (2015)

Time scales of transport in the embryonic lung.In the absence of flow, solutes can only diffuse (dotted curve). In the absence of diffusion, solutes and particles advect with the flow (dashed curve). Advection-diffusion (solid curve) transports solutes rapidly relative to diffusion alone, and a small occlusion from weak airway peristalsis can yield a dramatic reduction in transport time. 100 kDa globular protein in lumen fluid of measured viscosity 0.016 Pa-s.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493131&req=5

pone.0132015.g007: Time scales of transport in the embryonic lung.In the absence of flow, solutes can only diffuse (dotted curve). In the absence of diffusion, solutes and particles advect with the flow (dashed curve). Advection-diffusion (solid curve) transports solutes rapidly relative to diffusion alone, and a small occlusion from weak airway peristalsis can yield a dramatic reduction in transport time. 100 kDa globular protein in lumen fluid of measured viscosity 0.016 Pa-s.
Mentions: When AP begins, it is weak, and occlusions are small. The reflux velocity will be correspondingly smaller, and advection and diffusion interact in the intermediate range of Taylor dispersion [15, 16]. In this regime, solutes diffuse with an effective diffusion coefficient , where a is the lumen radius, bounded by the molecular diffusion coefficient D, giving (Fig 7). For example, for a 100 kDa globular protein in the embryonic lung lumen with viscosity 0.016 Pa-s and tubule inner radius 25 μm, the time scale to diffuse 100 μm is 30 minutes, but 1 mm takes 2 days. With a peristaltic wave at 50 μm/s and just 10% occlusion, yielding μm/s, that 100 kDa protein is transported 1 mm in an hour instead of 2 days, because of the interaction between advection and diffusion.

Bottom Line: The sensation of internal fluid flows has been shown to have potent morphogenetic effects, as has the transport of morphogens.We hypothesize that these effects play an important role in lung morphogenesis.We analyzed the interaction between the internal flows and diffusion and conclude that AP has a strong effect on flow sensing away from the tip and on transport of morphogens.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical Engineering, North Carolina State University, Raleigh, North Carolina, United States of America.

ABSTRACT
Epithelial organs are almost universally secretory. The lung secretes mucus of extremely variable consistency. In the early prenatal period, the secretions are of largely unknown composition, consistency, and flow rates. In addition to net outflow from secretion, the embryonic lung exhibits transient reversing flows from peristalsis. Airway peristalsis (AP) begins as soon as the smooth muscle forms, and persists until birth. Since the prenatal lung is liquid-filled, smooth muscle action can transport fluid far from the immediately adjacent tissues. The sensation of internal fluid flows has been shown to have potent morphogenetic effects, as has the transport of morphogens. We hypothesize that these effects play an important role in lung morphogenesis. To test these hypotheses in a quantitative framework, we analyzed the fluid-structure interactions between embryonic tissues and lumen fluid resulting from peristaltic waves that partially occlude the airway. We found that if the airway is closed, fluid transport is minimal; by contrast, if the trachea is open, shear rates can be very high, particularly at the stenosis. We performed a parametric analysis of flow characteristics' dependence on tissue stiffnesses, smooth muscle force, geometry, and fluid viscosity, and found that most of these relationships are governed by simple ratios. We measured the viscosity of prenatal lung fluid with passive bead microrheology. This paper reports the first measurements of the viscosity of embryonic lung lumen fluid. In the range tested, lumen fluid can be considered Newtonian, with a viscosity of 0.016 ± 0.008 Pa-s. We analyzed the interaction between the internal flows and diffusion and conclude that AP has a strong effect on flow sensing away from the tip and on transport of morphogens. These effects may be the intermediate mechanisms for the enhancement of branching seen in occluded embryonic lungs.

No MeSH data available.


Related in: MedlinePlus