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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

Estimates of reflux velocity and pressure.A. Partial occlusion moving distally pushes fluid proximally (reflux), and creates a pressure gradient across the stenosis. B. At the stenosis, average reflux velocity  is proportional to velocity of peristaltic wave vper, but increases rapidly with occlusion (dashed curve). Pressure gradient across the stenosis is proportional to fluid viscosity μ and strongly depends on occlusion O: , where a is the relaxed lumen radius (solid curve).
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pone.0132015.g002: Estimates of reflux velocity and pressure.A. Partial occlusion moving distally pushes fluid proximally (reflux), and creates a pressure gradient across the stenosis. B. At the stenosis, average reflux velocity is proportional to velocity of peristaltic wave vper, but increases rapidly with occlusion (dashed curve). Pressure gradient across the stenosis is proportional to fluid viscosity μ and strongly depends on occlusion O: , where a is the relaxed lumen radius (solid curve).

Mentions: Although the smooth muscle contracts in the same manner, AP moves lumen fluid very differently in the cases of complete occlusion (CO) and partial occlusion (PO). Most significantly, the direction of flow is different in CO and PO: For CO, fluid moves with the peristaltic wave, reversing only when the wave is released. For PO, fluid moves counter to the peristaltic wave (Fig 2A), reversing when the wave is released. For CO, the tissue deformations may be very large due to pressure buildup distal to the occlusion [4, 5]. Although tissue deformations can be large in CO, fluid flow rates are small, and there is virtually no fluid shear once occlusion is complete. In contrast, for PO, the tissue deformations are smaller, but the flow past the stenosis is substantial. Because flows from CO are small, in this paper, we focus our analysis of flows only on those driven by partial occlusion.


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)

Estimates of reflux velocity and pressure.A. Partial occlusion moving distally pushes fluid proximally (reflux), and creates a pressure gradient across the stenosis. B. At the stenosis, average reflux velocity  is proportional to velocity of peristaltic wave vper, but increases rapidly with occlusion (dashed curve). Pressure gradient across the stenosis is proportional to fluid viscosity μ and strongly depends on occlusion O: , where a is the relaxed lumen radius (solid curve).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132015.g002: Estimates of reflux velocity and pressure.A. Partial occlusion moving distally pushes fluid proximally (reflux), and creates a pressure gradient across the stenosis. B. At the stenosis, average reflux velocity is proportional to velocity of peristaltic wave vper, but increases rapidly with occlusion (dashed curve). Pressure gradient across the stenosis is proportional to fluid viscosity μ and strongly depends on occlusion O: , where a is the relaxed lumen radius (solid curve).
Mentions: Although the smooth muscle contracts in the same manner, AP moves lumen fluid very differently in the cases of complete occlusion (CO) and partial occlusion (PO). Most significantly, the direction of flow is different in CO and PO: For CO, fluid moves with the peristaltic wave, reversing only when the wave is released. For PO, fluid moves counter to the peristaltic wave (Fig 2A), reversing when the wave is released. For CO, the tissue deformations may be very large due to pressure buildup distal to the occlusion [4, 5]. Although tissue deformations can be large in CO, fluid flow rates are small, and there is virtually no fluid shear once occlusion is complete. In contrast, for PO, the tissue deformations are smaller, but the flow past the stenosis is substantial. Because flows from CO are small, in this paper, we focus our analysis of flows only on those driven by partial occlusion.

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