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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

Frames from model simulations of AP with partial occlusion, for open and closed trachea.Each frame shows half the symmetric tubule. A. Closed trachea. Lumen pressure is spatially uniform and increases as soon as AP begins. B. Open trachea. Lumen pressure is negligible until occlusion is almost complete. Pressure is uniform everywhere in the lumen except at stenosis, where flow is fastest. Maximal occlusion shown ~ 90%. C. Detail of open-trachea AP. Maximal occlusion precedes maximal pressure. Pressure distal to pinch forces fluid leakage and reduces occlusion as wave moves distally. Identical parameters (stiffness, viscosity, force input). Frames every 1.0 sec (A, B) and 0.5 sec (C).
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pone.0132015.g003: Frames from model simulations of AP with partial occlusion, for open and closed trachea.Each frame shows half the symmetric tubule. A. Closed trachea. Lumen pressure is spatially uniform and increases as soon as AP begins. B. Open trachea. Lumen pressure is negligible until occlusion is almost complete. Pressure is uniform everywhere in the lumen except at stenosis, where flow is fastest. Maximal occlusion shown ~ 90%. C. Detail of open-trachea AP. Maximal occlusion precedes maximal pressure. Pressure distal to pinch forces fluid leakage and reduces occlusion as wave moves distally. Identical parameters (stiffness, viscosity, force input). Frames every 1.0 sec (A, B) and 0.5 sec (C).

Mentions: Flow is coupled to a pressure gradient. If the trachea is closed, the pressure is spatially uniform (Fig 3A, S1 Video). If the trachea is open, pressure is low proximal to the stenosis and higher distal to it (Figs 1B and 3B, S2 Video). Pressure is uniform distal to the stenosis because there is essentially no flow there. At the stenosis, the flow velocity depends on the occlusion, so, , where is the local average velocity, vmid the midline velocity, a the initial tube radius, O the occlusion, and μ the viscosity [6].


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)

Frames from model simulations of AP with partial occlusion, for open and closed trachea.Each frame shows half the symmetric tubule. A. Closed trachea. Lumen pressure is spatially uniform and increases as soon as AP begins. B. Open trachea. Lumen pressure is negligible until occlusion is almost complete. Pressure is uniform everywhere in the lumen except at stenosis, where flow is fastest. Maximal occlusion shown ~ 90%. C. Detail of open-trachea AP. Maximal occlusion precedes maximal pressure. Pressure distal to pinch forces fluid leakage and reduces occlusion as wave moves distally. Identical parameters (stiffness, viscosity, force input). Frames every 1.0 sec (A, B) and 0.5 sec (C).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132015.g003: Frames from model simulations of AP with partial occlusion, for open and closed trachea.Each frame shows half the symmetric tubule. A. Closed trachea. Lumen pressure is spatially uniform and increases as soon as AP begins. B. Open trachea. Lumen pressure is negligible until occlusion is almost complete. Pressure is uniform everywhere in the lumen except at stenosis, where flow is fastest. Maximal occlusion shown ~ 90%. C. Detail of open-trachea AP. Maximal occlusion precedes maximal pressure. Pressure distal to pinch forces fluid leakage and reduces occlusion as wave moves distally. Identical parameters (stiffness, viscosity, force input). Frames every 1.0 sec (A, B) and 0.5 sec (C).
Mentions: Flow is coupled to a pressure gradient. If the trachea is closed, the pressure is spatially uniform (Fig 3A, S1 Video). If the trachea is open, pressure is low proximal to the stenosis and higher distal to it (Figs 1B and 3B, S2 Video). Pressure is uniform distal to the stenosis because there is essentially no flow there. At the stenosis, the flow velocity depends on the occlusion, so, , where is the local average velocity, vmid the midline velocity, a the initial tube radius, O the occlusion, and μ the viscosity [6].

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