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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

Geometry of embryonic lung and model.A. Explanted E11.5 mouse lung showing lumen (l), epithelium (e, green), and mesenchyme (m, red). Smooth muscle (sm) not visible. B. Embryonic lung idealized as unbranched, axisymmetric tubule, with three uniform tissue layers plus lumen. Smooth muscle undergoes active circumferential contraction wave (red), propagating distally, building lumen pressure ahead of it (blue).
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pone.0132015.g001: Geometry of embryonic lung and model.A. Explanted E11.5 mouse lung showing lumen (l), epithelium (e, green), and mesenchyme (m, red). Smooth muscle (sm) not visible. B. Embryonic lung idealized as unbranched, axisymmetric tubule, with three uniform tissue layers plus lumen. Smooth muscle undergoes active circumferential contraction wave (red), propagating distally, building lumen pressure ahead of it (blue).

Mentions: Lung lumen fluid is moved by secretion, airway peristalsis (AP) and, later, fetal breathing movements. Airway peristalsis and tonic contractions begin as soon as airway smooth muscle (SM) forms. AP is initially weak and uncoordinated, but settles into a rhythmic wave moving proximodistally [3] (Fig 1). It has been proposed that AP regulates lung morphogenesis, through tissue stretch [3], the magnitude and direction of which have been quantified [4, 5]. We here propose that the fluid flow generated by AP may itself be significant in prenatal lung development, in several different ways.


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)

Geometry of embryonic lung and model.A. Explanted E11.5 mouse lung showing lumen (l), epithelium (e, green), and mesenchyme (m, red). Smooth muscle (sm) not visible. B. Embryonic lung idealized as unbranched, axisymmetric tubule, with three uniform tissue layers plus lumen. Smooth muscle undergoes active circumferential contraction wave (red), propagating distally, building lumen pressure ahead of it (blue).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132015.g001: Geometry of embryonic lung and model.A. Explanted E11.5 mouse lung showing lumen (l), epithelium (e, green), and mesenchyme (m, red). Smooth muscle (sm) not visible. B. Embryonic lung idealized as unbranched, axisymmetric tubule, with three uniform tissue layers plus lumen. Smooth muscle undergoes active circumferential contraction wave (red), propagating distally, building lumen pressure ahead of it (blue).
Mentions: Lung lumen fluid is moved by secretion, airway peristalsis (AP) and, later, fetal breathing movements. Airway peristalsis and tonic contractions begin as soon as airway smooth muscle (SM) forms. AP is initially weak and uncoordinated, but settles into a rhythmic wave moving proximodistally [3] (Fig 1). It has been proposed that AP regulates lung morphogenesis, through tissue stretch [3], the magnitude and direction of which have been quantified [4, 5]. We here propose that the fluid flow generated by AP may itself be significant in prenatal lung development, in several different ways.

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