title: Chondrocyte deformation induces mitochondrial distortion and heterogeneous intracellular strain fields.
abstract: Chondrocyte mechanotransduction is poorly understood but may involve cell deformation and associated distortion of intracellular structures and organelles. This study quantifies the intracellular displacement and strain fields associated with chondrocyte deformation and in particular the distortion of the mitochondria network, which may have a role in mechanotransduction. Isolated articular chondrocytes were compressed in agarose constructs and simultaneously visualised using confocal microscopy. An optimised digital image correlation technique was developed to calculate the local intracellular displacement and strain fields using confocal images of fluorescently labelled mitochondria. The mitochondria formed a dynamic fibrous network or reticulum, which co-localised with microtubules and vimentin intermediate filaments. Cell deformation induced distortion of the mitochondria, which collapsed in the axis of compression with a resulting loss of volume. Compression generated heterogeneous intracellular strain fields indicating mechanical heterogeneity within the cytoplasm. The study provides evidence supporting the potential involvement of mitochondrial deformation in chondrocyte mechanotransduction, possibly involving strain-mediated release of reactive oxygen species. Furthermore the heterogeneous strain fields, which appear to be influenced by intracellular structure and organisation, may generate significant heterogeneity in mechanotransduction behaviour for cells subjected to identical levels of deformation.
authors.affiliation: Medical Engineering Division, Dept. of Engineering and IRC in Biomedical Materials, Queen Mary University of London, London, UK. m.m.knight@qmul.ac.uk
authors.forename: M M
authors.initials: MM
authors.lastname: Knight
authors.forename: Z
authors.initials: Z
authors.lastname: Bomzon
authors.forename: E
authors.initials: E
authors.lastname: Kimmel
authors.forename: A M
authors.initials: AM
authors.lastname: Sharma
authors.forename: D A
authors.initials: DA
authors.lastname: Lee
authors.forename: D L
authors.initials: DL
authors.lastname: Bader
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000502:physiology; D002417:Cattle; D018929:Cell Culture Techniques; D048430:Cell Shape; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000502:physiology*; D019245:Compressive Strength; D003599:Cytoskeleton / Q000502:physiology; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology; D050279:Metacarpal Bones / Q000166:cytology; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000502:physiology*; D012685:Sepharose / Q000502:physiology; D013997:Time Factors
chemical_list: D012685:Sepharose