Journal
ANNALS OF BIOMEDICAL ENGINEERING
Volume 50, Issue 1, Pages 39-55Publisher
SPRINGER
DOI: 10.1007/s10439-021-02900-1
Keywords
Articular cartilage; Laser scanning microscopy; Pericellular matrix; Chondrocyte; Multiscale model
Categories
Funding
- Canadian Institutes of Health Research
- Canada Research Chair Program
- Killam Foundation
- Alberta Innovates
- Natural Sciences and Engineering Research Council of Canada [RGPIN-2015-06027]
- Marie Skodowska-Curie Individual fellowship [890936]
- Marie Curie Actions (MSCA) [890936] Funding Source: Marie Curie Actions (MSCA)
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PCM asymmetry may play an important role in cartilage development, pathology, and engineering. The changes in PCM geometry can affect the cellular mechanical environment and the surface strains on cells.
The specialized pericellular matrix (PCM) surrounding chondrocytes within articular cartilage is critical to the tissue's health and longevity. Growing evidence suggests that PCM alterations are ubiquitous across all trajectories of osteoarthritis, a crippling and prevalent joint disease. The PCM geometry is of particular interest as it influences the cellular mechanical environment. Observations of asymmetrical PCM thickness have been reported, but a quantified characterization is lacking. To this end, a novel microscopy protocol was developed and applied to acquire images of the PCM surrounding live cells. Morphometric analysis indicated a statistical bias towards thicker PCM on the inferior cellular surface. The mechanical effects of this bias were investigated with multiscale modelling, which revealed potentially damaging, high tensile strains in the direction perpendicular to the membrane and localized on the inferior surface. These strains varied substantially between PCM asymmetry cases. Simulations with a thicker inferior PCM, representative of the observed geometry, resulted in strain magnitudes approximately half of those calculated for a symmetric geometry, and a third of those with a thin inferior PCM. This strain attenuation suggests that synthesis of a thicker inferior PCM may be a protective adaptation. PCM asymmetry may thus be important in cartilage development, pathology, and engineering.
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