Biomechanics of single chondrocytes under direct shear

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 (approximately 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.

On the role of the actin cytoskeleton and nucleus in the biomechanical response of spread cells

“…a unique set of passive material properties cannot be identified for a cell. The significant contribution of the actin cytoskeleton to the mechanical response of cells has been demonstrated in numerous experimental studies [17,18]. It has recently been demonstrated that a computational cell model must include the key features of remodelling and contractility of the actin cytoskeleton in order to provide a realistic prediction of cell biomechanical response to physical stimuli [18][19][20][21][22].…”

The effect of remodelling and contractility of the actin cytoskeleton on the shear resistance of single cells: a computational and experimental investigation

“…The glass substrate containing the cells was then placed in a Petri dish on an inverted microscope. A shear deformation was applied to individual cells by a tungsten probe [22]. Initially, the probe was positioned adjacent to the cell, 4 mm above the substrate (figure 1a).…”

Simulation of the Mechanical Response of Cells on Micropost Substrates

“…These microarrays have been used to study the adhesion and contractility of static cells [8,10] cells subjected to local [11] and global applied deformation [12], cell migration [13,14], and cell -cell adhesion [15]. Micropost arrays provide detailed quantitative data about the contractility of cells and measure tractions at a number of points on the cell [8], in contrast to whole-cell measurements obtained from atomic force microscopy or cell probing [16][17][18]. Numerous different designs of these arrays exist, with variations in the length and diameter of the pillars, the spacing between pillars, and the arrangement in square or triangular patterns.…”