Effect of Supercoiling on the Mechanical and Permeability Properties of Model Collagen IV Networks

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Abstract

Collagen IV networks in the glomerular basement membrane (GBM) are essential for the maintenance and regulation of blood filtration in the kidneys. The GBM contains two different types of collagen IV networks: [α1(IV)]2α2(IV) and α3(IV)α4(IV)α5(IV), the latter of which has a higher number of supercoils (two or more collagens coiling around each other). To investigate the effects of supercoiling on the mechanical and permeability properties of collagen IV networks, we generated model collagen IV networks in the GBM and reconnected them to create different levels of supercoiling. We found that supercoiling greatly increases the stiffness of collagen IV networks but only minimally decreases the permeability. Also, doubling the amount of supercoils in a network had a bigger effect than doubling the stiffness of the supercoils. Our results suggest that the formation of supercoils is a specialized mechanism by the GBM that provides with a network stiff and strong enough to withstand the high hydrostatic pressures of filtration, yet porous enough that filtration is not hindered. Clinically, understanding the effects of supercoiling gives us insight into the mechanisms of GBM failure in some disease states where the normal collagen IV structure is disrupted.

Original languageEnglish (US)
Pages (from-to)1695-1705
Number of pages11
JournalAnnals of Biomedical Engineering
Volume43
Issue number7
DOIs
StatePublished - Jul 22 2015

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Collagen
Stiffness
Hydrostatic pressure
Blood
Basement Membrane

Keywords

  • Alport syndrome
  • Biomechanics
  • Glomerular basement membrane
  • Type IV collagen

Cite this

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title = "Effect of Supercoiling on the Mechanical and Permeability Properties of Model Collagen IV Networks",
abstract = "Collagen IV networks in the glomerular basement membrane (GBM) are essential for the maintenance and regulation of blood filtration in the kidneys. The GBM contains two different types of collagen IV networks: [α1(IV)]2α2(IV) and α3(IV)α4(IV)α5(IV), the latter of which has a higher number of supercoils (two or more collagens coiling around each other). To investigate the effects of supercoiling on the mechanical and permeability properties of collagen IV networks, we generated model collagen IV networks in the GBM and reconnected them to create different levels of supercoiling. We found that supercoiling greatly increases the stiffness of collagen IV networks but only minimally decreases the permeability. Also, doubling the amount of supercoils in a network had a bigger effect than doubling the stiffness of the supercoils. Our results suggest that the formation of supercoils is a specialized mechanism by the GBM that provides with a network stiff and strong enough to withstand the high hydrostatic pressures of filtration, yet porous enough that filtration is not hindered. Clinically, understanding the effects of supercoiling gives us insight into the mechanisms of GBM failure in some disease states where the normal collagen IV structure is disrupted.",
keywords = "Alport syndrome, Biomechanics, Glomerular basement membrane, Type IV collagen",
author = "Lazarina Gyoneva and Yoav Segal and Dorfman, {Kevin D.} and Barocas, {Victor H.}",
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T1 - Effect of Supercoiling on the Mechanical and Permeability Properties of Model Collagen IV Networks

AU - Gyoneva, Lazarina

AU - Segal, Yoav

AU - Dorfman, Kevin D.

AU - Barocas, Victor H.

PY - 2015/7/22

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N2 - Collagen IV networks in the glomerular basement membrane (GBM) are essential for the maintenance and regulation of blood filtration in the kidneys. The GBM contains two different types of collagen IV networks: [α1(IV)]2α2(IV) and α3(IV)α4(IV)α5(IV), the latter of which has a higher number of supercoils (two or more collagens coiling around each other). To investigate the effects of supercoiling on the mechanical and permeability properties of collagen IV networks, we generated model collagen IV networks in the GBM and reconnected them to create different levels of supercoiling. We found that supercoiling greatly increases the stiffness of collagen IV networks but only minimally decreases the permeability. Also, doubling the amount of supercoils in a network had a bigger effect than doubling the stiffness of the supercoils. Our results suggest that the formation of supercoils is a specialized mechanism by the GBM that provides with a network stiff and strong enough to withstand the high hydrostatic pressures of filtration, yet porous enough that filtration is not hindered. Clinically, understanding the effects of supercoiling gives us insight into the mechanisms of GBM failure in some disease states where the normal collagen IV structure is disrupted.

AB - Collagen IV networks in the glomerular basement membrane (GBM) are essential for the maintenance and regulation of blood filtration in the kidneys. The GBM contains two different types of collagen IV networks: [α1(IV)]2α2(IV) and α3(IV)α4(IV)α5(IV), the latter of which has a higher number of supercoils (two or more collagens coiling around each other). To investigate the effects of supercoiling on the mechanical and permeability properties of collagen IV networks, we generated model collagen IV networks in the GBM and reconnected them to create different levels of supercoiling. We found that supercoiling greatly increases the stiffness of collagen IV networks but only minimally decreases the permeability. Also, doubling the amount of supercoils in a network had a bigger effect than doubling the stiffness of the supercoils. Our results suggest that the formation of supercoils is a specialized mechanism by the GBM that provides with a network stiff and strong enough to withstand the high hydrostatic pressures of filtration, yet porous enough that filtration is not hindered. Clinically, understanding the effects of supercoiling gives us insight into the mechanisms of GBM failure in some disease states where the normal collagen IV structure is disrupted.

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KW - Biomechanics

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KW - Type IV collagen

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