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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

Velocity and shear rate.Lumen fluid velocity at the midline (solid curves) and shear rate at the lumen surface (dashed curves) track each other in time (horiz. axis). Curves correspond to locations on airway at left. Red dots indicate location, relative magnitude, and time of SM force peak. Each curve shows time series of fluid velocity and shear rate. Maximal flow at a position occurs slightly after maximal SM force at that position. Flow is fastest towards trachea, opposite the direction of peristaltic SM wave; refilling flows are slower. Flow distal to SM is negligible. Flow is dramatically reduced in the closed-end airway.
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pone.0132015.g004: Velocity and shear rate.Lumen fluid velocity at the midline (solid curves) and shear rate at the lumen surface (dashed curves) track each other in time (horiz. axis). Curves correspond to locations on airway at left. Red dots indicate location, relative magnitude, and time of SM force peak. Each curve shows time series of fluid velocity and shear rate. Maximal flow at a position occurs slightly after maximal SM force at that position. Flow is fastest towards trachea, opposite the direction of peristaltic SM wave; refilling flows are slower. Flow distal to SM is negligible. Flow is dramatically reduced in the closed-end airway.

Mentions: A closed trachea blocks flow out of the lung, so flow inside the lung is substantially reduced. Because a closed trachea does not permit pressure release, lumen pressure is spatially uniform, and occlusion is substantially reduced for the same SM force (Fig 3, S1 Video, Fig 4). If the trachea is open, flow is substantial within the lung, flow is substantial exiting the lung, occlusion is greater, and flow and pressure gradients at the stenosis can be very large (Fig 3, S2 Video, Fig 4).


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)

Velocity and shear rate.Lumen fluid velocity at the midline (solid curves) and shear rate at the lumen surface (dashed curves) track each other in time (horiz. axis). Curves correspond to locations on airway at left. Red dots indicate location, relative magnitude, and time of SM force peak. Each curve shows time series of fluid velocity and shear rate. Maximal flow at a position occurs slightly after maximal SM force at that position. Flow is fastest towards trachea, opposite the direction of peristaltic SM wave; refilling flows are slower. Flow distal to SM is negligible. Flow is dramatically reduced in the closed-end airway.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132015.g004: Velocity and shear rate.Lumen fluid velocity at the midline (solid curves) and shear rate at the lumen surface (dashed curves) track each other in time (horiz. axis). Curves correspond to locations on airway at left. Red dots indicate location, relative magnitude, and time of SM force peak. Each curve shows time series of fluid velocity and shear rate. Maximal flow at a position occurs slightly after maximal SM force at that position. Flow is fastest towards trachea, opposite the direction of peristaltic SM wave; refilling flows are slower. Flow distal to SM is negligible. Flow is dramatically reduced in the closed-end airway.
Mentions: A closed trachea blocks flow out of the lung, so flow inside the lung is substantially reduced. Because a closed trachea does not permit pressure release, lumen pressure is spatially uniform, and occlusion is substantially reduced for the same SM force (Fig 3, S1 Video, Fig 4). If the trachea is open, flow is substantial within the lung, flow is substantial exiting the lung, occlusion is greater, and flow and pressure gradients at the stenosis can be very large (Fig 3, S2 Video, Fig 4).

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