Biophysical properties of normal and diseased renal glomeruli.
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 Tg26(HIV/nl) mice (HIV-associated nephropathy model), at stages where glomerular injury was minimal by histopathology. Col4a3(-/-) mice express abnormal glomerular basement membrane proteins, and Tg26(HIV/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.
Physics, Harvard University, Cambridge, Massachusetts, USA.
Hans M
HM
Wyss
Joel M
JM
Henderson
Fitzroy J
FJ
Byfield
Leslie A
LA
Bruggeman
Yaxian
Y
Ding
Chunfa
C
Huang
Jung Hee
JH
Suh
Thomas
T
Franke
Elisa
E
Mele
Martin R
MR
Pollak
Jeffrey H
JH
Miner
Paul A
PA
Janmey
David A
DA
Weitz
R Tyler
RT
Miller
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001324:Autoantigens / Q000235:genetics; D024141:Collagen Type IV / Q000172:deficiency / Q000235:genetics; D055119:Elastic Modulus / Q000187:drug effects / Q000502:physiology*; D004548:Elasticity / Q000187:drug effects / Q000502:physiology*; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051381:Rats; D017207:Rats, Sprague-Dawley
D001324:Autoantigens; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain