Chondrocyte mechanotransduction: effects of compression on deformation of intracellular organelles and relevance to cellular biosynthesis.
OBJECTIVE
The effects of mechanical deformation of intact cartilage tissue on chondrocyte biosynthesis in situ have been well documented, but the mechanotransduction pathways that regulate such phenomena have not been elucidated completely. The goal of this study was to examine the effects of tissue deformation on the morphology of a range of intracellular organelles which play a major role in cell biosynthesis and metabolism.


METHODS
Using chemical fixation, high pressure freezing, and electron microscopy, we imaged chondrocytes within mechanically compressed cartilage explants at high magnification and quantitatively and qualitatively assessed changes in organelle volume and shape caused by graded levels of loading.


RESULTS
Compression of the tissue caused a concomitant reduction in the volume of the extracellular matrix (ECM), chondrocyte, nucleus, rough endoplasmic reticulum, and mitochondria. Interestingly, however, the Golgi apparatus was able to resist loss of intraorganelle water and retain a portion of its volume relative to the remainder of the cell. These combined results suggest that a balance between intracellular mechanical and osmotic gradients govern the changes in shape and volume of the organelles as the tissue is compressed.


CONCLUSIONS
Our results lead to the interpretive hypothesis that organelle volume changes appear to be driven mainly by osmotic interactions while shape changes are mediated by structural factors, such as cytoskeletal interactions that may be linked to extracellular matrix deformations. The observed volume and shape changes of the chondrocyte organelles and the differential behavior between organelles during tissue compression provide evidence for an important mechanotransduction pathway linking translational and post-translational events (e.g., elongation and sulfation of glycosaminoglycans (GAGs) in the Golgi) to cell deformation.
Szafranski
Jon D
JD
Biological Engineering Division and Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Grodzinsky
Alan J
AJ
Burger
Elke
E
Gaschen
Veronique
V
Hung
Han-Hwa
HH
Hunziker
Ernst B
EB
D000818:Animals; D002417:Cattle; D048430:Cell Shape; D048429:Cell Size; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000648:ultrastructure; D005615:Freezing; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008854:Microscopy, Electron; D015388:Organelles / Q000378:metabolism* / Q000648:ultrastructure; D009997:Osmotic Pressure; D011312:Pressure