Biomechanics of single chondrocytes under direct shear |
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Authors: | Gidon Ofek Enda P Dowling Robert M Raphael J Patrick McGarry Kyriacos A Athanasiou |
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Affiliation: | (1) Department of Mechanical and Biomedical Engineering, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland |
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Abstract: | Articular chondrocytes experience a variety of mechanical stimuli during daily activity. One such stimulus, direct shear,
is known to affect chondrocyte homeostasis and induce catabolic or anabolic pathways. Understanding how single chondrocytes
respond biomechanically and morphologically to various levels of applied shear is an important first step toward elucidating
tissue level responses and disease etiology. To this end, a novel videocapture method was developed in this study to examine
the effect of direct shear on single chondrocytes, applied via the controlled lateral displacement of a shearing probe. Through
this approach, precise force and deformation measurements could be obtained during the shear event, as well as clear pictures
of the initial cell-to-probe contact configuration. To further study the non-uniform shear characteristics of single chondrocytes,
the probe was positioned in three different placement ranges along the cell height. It was observed that the apparent shear
modulus of single chondrocytes decreased as the probe transitioned from being close to the cell base (4.1 ± 1.3 kPa), to the
middle of the cell (2.6 ± 1.1 kPa), and then near its top (1.7 ± 0.8 kPa). In addition, cells experienced the greatest peak
forward displacement (~30% of their initial diameter) when the probe was placed low, near the base. Forward cell movement
during shear, regardless of its magnitude, continued until it reached a plateau at ~35% shear strain for all probe positions,
suggesting that focal adhesions become activated at this shear level to firmly adhere the cell to its substrate. Based on
intracellular staining, the observed height-specific variation in cell shear stiffness and plateau in forward cell movement
appeared to be due to a rearrangement of focal adhesions and actin at higher shear strains. Understanding the fundamental
mechanisms at play during shear of single cells will help elucidate potential treatments for chondrocyte pathology and loading
regimens related to cartilage health and disease. |
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