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Hydraulic fracture during epithelial stretching.

Casares L, Vincent R, Zalvidea D, Campillo N, Navajas D, Arroyo M, Trepat X - Nat Mater (2015)

Bottom Line: Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension.We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres.Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics.

View Article: PubMed Central - PubMed

Affiliation: Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.

ABSTRACT
The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells' cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres. After pressure equilibration, cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics.

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Stretch induces poroelastic flows and pressure beneath the cell clustera, Illustration of the coupling between hydrogel stretching and swelling. Immediately after a rapid stretch or unstretch maneuver, the hydrogel volume is conserved. With time, the free energy balance in the hydrogel causes poroelastic flows that lead to progressive swelling or de-swelling of the hydrogel. b, Time evolution of PAA hydrogel thickness during and after stretch pulses of 1 s, 1 min, and 10 min (normalized to baseline levels). Stretch pulses were applied successively to each pattern, in a random order and spaced by >15 min (n=4 different patterns, error bars are SEM). c, Idealization of the gel underneath an epithelial cluster as a cylindrical region covered by a disc-like impermeable barrier (modeled epithelial clusters are 80 μm in diameter and the gel is 156 μm in thickness). This gel domain is modeled with the large deformation poroelastic theory (Supplementary Note 1). d, Axisymmetric finite element discretization of the system shown in (c). e, Solvent pressure and deformation of the gel during the stretch-unstretch maneuver in the presence of an impermeable disc-like barrier as predicted by the model. f, Solvent flow pattern near the edge of the epithelial cluster 6 s after stretch cessation. g, Solvent flow pattern near the edge of the epithelial cluster 6 s after stretch application.
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Figure 3: Stretch induces poroelastic flows and pressure beneath the cell clustera, Illustration of the coupling between hydrogel stretching and swelling. Immediately after a rapid stretch or unstretch maneuver, the hydrogel volume is conserved. With time, the free energy balance in the hydrogel causes poroelastic flows that lead to progressive swelling or de-swelling of the hydrogel. b, Time evolution of PAA hydrogel thickness during and after stretch pulses of 1 s, 1 min, and 10 min (normalized to baseline levels). Stretch pulses were applied successively to each pattern, in a random order and spaced by >15 min (n=4 different patterns, error bars are SEM). c, Idealization of the gel underneath an epithelial cluster as a cylindrical region covered by a disc-like impermeable barrier (modeled epithelial clusters are 80 μm in diameter and the gel is 156 μm in thickness). This gel domain is modeled with the large deformation poroelastic theory (Supplementary Note 1). d, Axisymmetric finite element discretization of the system shown in (c). e, Solvent pressure and deformation of the gel during the stretch-unstretch maneuver in the presence of an impermeable disc-like barrier as predicted by the model. f, Solvent flow pattern near the edge of the epithelial cluster 6 s after stretch cessation. g, Solvent flow pattern near the edge of the epithelial cluster 6 s after stretch application.

Mentions: The theory of poroelasticity has been successful at predicting the coupling between mechanics and solvent migration in a broad diversity of synthetic and physiological hydrogels34 including the cell cytoplasm20,35. The behavior of elastomeric hydrogels composed of flexible polymers undergoing large deformations, such as our PAA hydrogels, can be understood and quantified by recent theoretical advances36,37. The swelling state of the hydrogel is set by a balance between the mixing entropy of the system, which tends to attract solvent into the network, and the entropy of the polymer chains, which tends to expel solvent. Deformation affects the chemical potential of the solvent, thereby driving its diffusive flow. This theory predicts that an ideal hydrogel stretched laterally as in our experiments will initially thin down to preserve volume, and over a longer time-scale, will swell as a result of solvent influx (Fig. 3a). Conversely, when the hydrogel is unstretched or compressed, it will experience an increase in thickness followed by a gradual efflux of solvent (de-swelling). If the hydrogel is partially covered by an impermeable barrier, such as the tight epithelial islands in our experiments, solvent efflux will be blocked, leading to a local pressure increase across the barrier.


Hydraulic fracture during epithelial stretching.

Casares L, Vincent R, Zalvidea D, Campillo N, Navajas D, Arroyo M, Trepat X - Nat Mater (2015)

Stretch induces poroelastic flows and pressure beneath the cell clustera, Illustration of the coupling between hydrogel stretching and swelling. Immediately after a rapid stretch or unstretch maneuver, the hydrogel volume is conserved. With time, the free energy balance in the hydrogel causes poroelastic flows that lead to progressive swelling or de-swelling of the hydrogel. b, Time evolution of PAA hydrogel thickness during and after stretch pulses of 1 s, 1 min, and 10 min (normalized to baseline levels). Stretch pulses were applied successively to each pattern, in a random order and spaced by >15 min (n=4 different patterns, error bars are SEM). c, Idealization of the gel underneath an epithelial cluster as a cylindrical region covered by a disc-like impermeable barrier (modeled epithelial clusters are 80 μm in diameter and the gel is 156 μm in thickness). This gel domain is modeled with the large deformation poroelastic theory (Supplementary Note 1). d, Axisymmetric finite element discretization of the system shown in (c). e, Solvent pressure and deformation of the gel during the stretch-unstretch maneuver in the presence of an impermeable disc-like barrier as predicted by the model. f, Solvent flow pattern near the edge of the epithelial cluster 6 s after stretch cessation. g, Solvent flow pattern near the edge of the epithelial cluster 6 s after stretch application.
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Related In: Results  -  Collection

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Figure 3: Stretch induces poroelastic flows and pressure beneath the cell clustera, Illustration of the coupling between hydrogel stretching and swelling. Immediately after a rapid stretch or unstretch maneuver, the hydrogel volume is conserved. With time, the free energy balance in the hydrogel causes poroelastic flows that lead to progressive swelling or de-swelling of the hydrogel. b, Time evolution of PAA hydrogel thickness during and after stretch pulses of 1 s, 1 min, and 10 min (normalized to baseline levels). Stretch pulses were applied successively to each pattern, in a random order and spaced by >15 min (n=4 different patterns, error bars are SEM). c, Idealization of the gel underneath an epithelial cluster as a cylindrical region covered by a disc-like impermeable barrier (modeled epithelial clusters are 80 μm in diameter and the gel is 156 μm in thickness). This gel domain is modeled with the large deformation poroelastic theory (Supplementary Note 1). d, Axisymmetric finite element discretization of the system shown in (c). e, Solvent pressure and deformation of the gel during the stretch-unstretch maneuver in the presence of an impermeable disc-like barrier as predicted by the model. f, Solvent flow pattern near the edge of the epithelial cluster 6 s after stretch cessation. g, Solvent flow pattern near the edge of the epithelial cluster 6 s after stretch application.
Mentions: The theory of poroelasticity has been successful at predicting the coupling between mechanics and solvent migration in a broad diversity of synthetic and physiological hydrogels34 including the cell cytoplasm20,35. The behavior of elastomeric hydrogels composed of flexible polymers undergoing large deformations, such as our PAA hydrogels, can be understood and quantified by recent theoretical advances36,37. The swelling state of the hydrogel is set by a balance between the mixing entropy of the system, which tends to attract solvent into the network, and the entropy of the polymer chains, which tends to expel solvent. Deformation affects the chemical potential of the solvent, thereby driving its diffusive flow. This theory predicts that an ideal hydrogel stretched laterally as in our experiments will initially thin down to preserve volume, and over a longer time-scale, will swell as a result of solvent influx (Fig. 3a). Conversely, when the hydrogel is unstretched or compressed, it will experience an increase in thickness followed by a gradual efflux of solvent (de-swelling). If the hydrogel is partially covered by an impermeable barrier, such as the tight epithelial islands in our experiments, solvent efflux will be blocked, leading to a local pressure increase across the barrier.

Bottom Line: Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension.We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres.Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics.

View Article: PubMed Central - PubMed

Affiliation: Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.

ABSTRACT
The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells' cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres. After pressure equilibration, cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics.

Show MeSH
Related in: MedlinePlus