Biophysical properties of normal and diseased renal glomeruli

Hans M. Wyss, Joel M. Henderson, Fitzroy J. Byfield, Leslie A. Bruggeman, Yaxian Ding, Chunfa Huang, Jung Hee Suh, Thomas Franke, Elisa Mele, Martin R. Pollak, Jeffrey H. Miner, Paul A. Janmey, David A. Weitz, R. Tyler Miller

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The mechanical properties of tissues and cells including renal glomeruli are important determinants of their differentiated state, function, and responses to injury but are not well characterized or understood. Understanding glomerular mechanics is important for understanding renal diseases attributable to abnormal expression or assembly of structural proteins and abnormal hemodynamics. We use atomic force microscopy (AFM) and a new technique, capillary micromechanics, to measure the elastic properties of rat glomeruli. The Young's modulus of glomeruli was 2,500 Pa, and it was reduced to 1,100 Pa by cytochalasin and latunculin, and to 1,400 Pa by blebbistatin. Cytochalasin or latrunculin reduced the F/G actin ratios of glomeruli but did not disrupt their architecture. To assess glomerular biomechanics in disease, we measured the Young's moduli of glomeruli from two mouse models of primary glomerular disease, Col4a3-/- mice (Alport model) and Tg26HIV/nl mice (HIV-associated nephropathy model), at stages where glomerular injury was minimal by histopathology. Col4a3-/- mice express abnormal glomerular basement membrane proteins, and Tg26HIV/nl mouse podocytes have multiple abnormalities in morphology, adhesion, and cytoskeletal structure. In both models, the Young's modulus of the glomeruli was reduced by 30%. We find that glomeruli have specific and quantifiable biomechanical properties that are dependent on the state of the actin cytoskeleton and nonmuscle myosins. These properties may be altered early in disease and represent an important early component of disease. This increased deformability of glomeruli could directly contribute to disease by permitting increased distension with hemodynamic force or represent a mechanically inhospitable environment for glomerular cells.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume300
Issue number3
DOIs
StatePublished - Mar 2011

Fingerprint

Kidney
Elastic Modulus
Cytochalasins
AIDS-Associated Nephropathy
Hemodynamics
Multiple Abnormalities
Podocytes
Glomerular Basement Membrane
Atomic Force Microscopy
Wounds and Injuries
Myosins
Mechanics
Actin Cytoskeleton
Biomechanical Phenomena
Actins
Membrane Proteins
Proteins

Keywords

  • Actin
  • Alport syndrome
  • Atomic force microscopy
  • Biophysics
  • Cytoskeleton
  • Glomerulus
  • HIV-associated neuropathy

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Biophysical properties of normal and diseased renal glomeruli. / Wyss, Hans M.; Henderson, Joel M.; Byfield, Fitzroy J.; Bruggeman, Leslie A.; Ding, Yaxian; Huang, Chunfa; Suh, Jung Hee; Franke, Thomas; Mele, Elisa; Pollak, Martin R.; Miner, Jeffrey H.; Janmey, Paul A.; Weitz, David A.; Miller, R. Tyler.

In: American Journal of Physiology - Cell Physiology, Vol. 300, No. 3, 03.2011.

Research output: Contribution to journalArticle

Wyss, HM, Henderson, JM, Byfield, FJ, Bruggeman, LA, Ding, Y, Huang, C, Suh, JH, Franke, T, Mele, E, Pollak, MR, Miner, JH, Janmey, PA, Weitz, DA & Miller, RT 2011, 'Biophysical properties of normal and diseased renal glomeruli', American Journal of Physiology - Cell Physiology, vol. 300, no. 3. https://doi.org/10.1152/ajpcell.00438.2010
Wyss, Hans M. ; Henderson, Joel M. ; Byfield, Fitzroy J. ; Bruggeman, Leslie A. ; Ding, Yaxian ; Huang, Chunfa ; Suh, Jung Hee ; Franke, Thomas ; Mele, Elisa ; Pollak, Martin R. ; Miner, Jeffrey H. ; Janmey, Paul A. ; Weitz, David A. ; Miller, R. Tyler. / Biophysical properties of normal and diseased renal glomeruli. In: American Journal of Physiology - Cell Physiology. 2011 ; Vol. 300, No. 3.
@article{45176d71630e4165964d7c56514de9b7,
title = "Biophysical properties of normal and diseased renal glomeruli",
abstract = "The mechanical properties of tissues and cells including renal glomeruli are important determinants of their differentiated state, function, and responses to injury but are not well characterized or understood. Understanding glomerular mechanics is important for understanding renal diseases attributable to abnormal expression or assembly of structural proteins and abnormal hemodynamics. We use atomic force microscopy (AFM) and a new technique, capillary micromechanics, to measure the elastic properties of rat glomeruli. The Young's modulus of glomeruli was 2,500 Pa, and it was reduced to 1,100 Pa by cytochalasin and latunculin, and to 1,400 Pa by blebbistatin. Cytochalasin or latrunculin reduced the F/G actin ratios of glomeruli but did not disrupt their architecture. To assess glomerular biomechanics in disease, we measured the Young's moduli of glomeruli from two mouse models of primary glomerular disease, Col4a3-/- mice (Alport model) and Tg26HIV/nl mice (HIV-associated nephropathy model), at stages where glomerular injury was minimal by histopathology. Col4a3-/- mice express abnormal glomerular basement membrane proteins, and Tg26HIV/nl mouse podocytes have multiple abnormalities in morphology, adhesion, and cytoskeletal structure. In both models, the Young's modulus of the glomeruli was reduced by 30{\%}. We find that glomeruli have specific and quantifiable biomechanical properties that are dependent on the state of the actin cytoskeleton and nonmuscle myosins. These properties may be altered early in disease and represent an important early component of disease. This increased deformability of glomeruli could directly contribute to disease by permitting increased distension with hemodynamic force or represent a mechanically inhospitable environment for glomerular cells.",
keywords = "Actin, Alport syndrome, Atomic force microscopy, Biophysics, Cytoskeleton, Glomerulus, HIV-associated neuropathy",
author = "Wyss, {Hans M.} and Henderson, {Joel M.} and Byfield, {Fitzroy J.} and Bruggeman, {Leslie A.} and Yaxian Ding and Chunfa Huang and Suh, {Jung Hee} and Thomas Franke and Elisa Mele and Pollak, {Martin R.} and Miner, {Jeffrey H.} and Janmey, {Paul A.} and Weitz, {David A.} and Miller, {R. Tyler}",
year = "2011",
month = "3",
doi = "10.1152/ajpcell.00438.2010",
language = "English (US)",
volume = "300",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Biophysical properties of normal and diseased renal glomeruli

AU - Wyss, Hans M.

AU - Henderson, Joel M.

AU - Byfield, Fitzroy J.

AU - Bruggeman, Leslie A.

AU - Ding, Yaxian

AU - Huang, Chunfa

AU - Suh, Jung Hee

AU - Franke, Thomas

AU - Mele, Elisa

AU - Pollak, Martin R.

AU - Miner, Jeffrey H.

AU - Janmey, Paul A.

AU - Weitz, David A.

AU - Miller, R. Tyler

PY - 2011/3

Y1 - 2011/3

N2 - The mechanical properties of tissues and cells including renal glomeruli are important determinants of their differentiated state, function, and responses to injury but are not well characterized or understood. Understanding glomerular mechanics is important for understanding renal diseases attributable to abnormal expression or assembly of structural proteins and abnormal hemodynamics. We use atomic force microscopy (AFM) and a new technique, capillary micromechanics, to measure the elastic properties of rat glomeruli. The Young's modulus of glomeruli was 2,500 Pa, and it was reduced to 1,100 Pa by cytochalasin and latunculin, and to 1,400 Pa by blebbistatin. Cytochalasin or latrunculin reduced the F/G actin ratios of glomeruli but did not disrupt their architecture. To assess glomerular biomechanics in disease, we measured the Young's moduli of glomeruli from two mouse models of primary glomerular disease, Col4a3-/- mice (Alport model) and Tg26HIV/nl mice (HIV-associated nephropathy model), at stages where glomerular injury was minimal by histopathology. Col4a3-/- mice express abnormal glomerular basement membrane proteins, and Tg26HIV/nl mouse podocytes have multiple abnormalities in morphology, adhesion, and cytoskeletal structure. In both models, the Young's modulus of the glomeruli was reduced by 30%. We find that glomeruli have specific and quantifiable biomechanical properties that are dependent on the state of the actin cytoskeleton and nonmuscle myosins. These properties may be altered early in disease and represent an important early component of disease. This increased deformability of glomeruli could directly contribute to disease by permitting increased distension with hemodynamic force or represent a mechanically inhospitable environment for glomerular cells.

AB - The mechanical properties of tissues and cells including renal glomeruli are important determinants of their differentiated state, function, and responses to injury but are not well characterized or understood. Understanding glomerular mechanics is important for understanding renal diseases attributable to abnormal expression or assembly of structural proteins and abnormal hemodynamics. We use atomic force microscopy (AFM) and a new technique, capillary micromechanics, to measure the elastic properties of rat glomeruli. The Young's modulus of glomeruli was 2,500 Pa, and it was reduced to 1,100 Pa by cytochalasin and latunculin, and to 1,400 Pa by blebbistatin. Cytochalasin or latrunculin reduced the F/G actin ratios of glomeruli but did not disrupt their architecture. To assess glomerular biomechanics in disease, we measured the Young's moduli of glomeruli from two mouse models of primary glomerular disease, Col4a3-/- mice (Alport model) and Tg26HIV/nl mice (HIV-associated nephropathy model), at stages where glomerular injury was minimal by histopathology. Col4a3-/- mice express abnormal glomerular basement membrane proteins, and Tg26HIV/nl mouse podocytes have multiple abnormalities in morphology, adhesion, and cytoskeletal structure. In both models, the Young's modulus of the glomeruli was reduced by 30%. We find that glomeruli have specific and quantifiable biomechanical properties that are dependent on the state of the actin cytoskeleton and nonmuscle myosins. These properties may be altered early in disease and represent an important early component of disease. This increased deformability of glomeruli could directly contribute to disease by permitting increased distension with hemodynamic force or represent a mechanically inhospitable environment for glomerular cells.

KW - Actin

KW - Alport syndrome

KW - Atomic force microscopy

KW - Biophysics

KW - Cytoskeleton

KW - Glomerulus

KW - HIV-associated neuropathy

UR - http://www.scopus.com/inward/record.url?scp=79952145533&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952145533&partnerID=8YFLogxK

U2 - 10.1152/ajpcell.00438.2010

DO - 10.1152/ajpcell.00438.2010

M3 - Article

VL - 300

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 3

ER -