A finite element model predicts the mechanotransduction response of tendon cells to cyclic tensile loading

Abstract

The importance of fluid-flow-induced shear stress and matrix-induced cell deformation in transmitting the global tendon load into a cellular mechanotransduction response is yet to be determined. A multiscale computational tendon model composed of both matrix and fluid phases was created to examine how global tendon loading may affect fluid-flow-induced shear stresses and membrane strains at the cellular level. The model was then used to develop a quantitative experiment to help understand the roles of membrane strains and fluid-induced shear stresses on the biological response of individual cells. The model was able to predict the global response of tendon to applied strain (stress, fluid exudation), as well as the associated cellular response of increased fluid-flow-induced shear stress with strain rate and matrix-induced cell deformation with strain amplitude. The model analysis, combined with the experimental results, demonstrated that both strain rate and strain amplitude are able to independently alter rat interstitial collagenase gene expression through increases in fluid-flow-induced shear stress and matrix-induced cell deformation, respectively.

Effect of in vitro stress‐deprivation and cyclic loading on the length of tendon cell cilia in situ

“…34 While these load induced alterations in gene expression in tendon cells cannot be directly attributed to a mechanosensory function of the primary cilium, the affects of loading have been associated with changes in cilia length. 9,18,21,31,32 Tensile loading of rat tail tendons has been shown to result in fluid flow, 25,26 and cellular deformations. 24 Both of these mechanisms have previously been associated with a decrease in cilia length.…”

“…22 Studies from our lab have shown that stress-deprivation (SD) of tendon cells has been associated with a disruption of cytoskeletal organization, 23 while tensile loading of tendons has been associated with cell deformation 24 and extracellular fluid flow. 25,26 Therefore, the purpose of the current study was to examine the effect of loading conditions on the length of primary cilia of rat tail tendon cells in situ. We hypothesize that (A) SD will increase the length of primary cilia on cells within a rat tail tendon and (B) cyclic tensile loading will reverse (shorten) tendon cell cilia lengthened in response to SD.…”

Human achilles tendon plasticity in response to cyclic strain: effect of rate and duration

“…of view, four factors of the applied strain may affect the adaptive response of tendons: magnitude, frequency, rate and duration (Arnoczky et al, 2002;Lavagnino et al, 2008;Yamamoto et al, 2005;Yamamoto et al, 2003;Yang et al, 2004). Recent experiments on the human Achilles tendon (AT) in vivo by our group showed that a high strain magnitude (4.5-5.0%) is required to trigger adaptive effects on the tendon mechanical, morphological and material properties (Arampatzis et al, 2010;Arampatzis et al, 2007).…”

“…The strain at the cellular level is much lower compared with the external tendon strain (Arnoczky et al, 2002;Screen et al, 2005). Two modes were suggested for the transmission of the external strain to the cellular level: cell deformation and fluid flow-induced shear stress (Lavagnino et al, 2003;Lavagnino et al, 2008). With increasing strain, a loss of collagen crimp and an increase in fiber recruitment was observed (Hansen et al, 2002;Schatzmann et al, 1998) and likely results in an increased number of cells being deformed (Arnoczky et al, 2002).…”

“…With increasing strain, a loss of collagen crimp and an increase in fiber recruitment was observed (Hansen et al, 2002;Schatzmann et al, 1998) and likely results in an increased number of cells being deformed (Arnoczky et al, 2002). The inhibition of catabolic cell responses (collagenase mRNA) seems to be directly associated with progressive increases of strain magnitude (Arnoczky et al, 2004;Lavagnino et al, 2008;Lavagnino et al, 2003). Furthermore, the extracellular matrix features viscous behavior due to the content of collagen and water, and interactions between collagenous and non-collagenous properties (Ciarletta and Ben Amar, 2009;, and, thus, a time-dependent transmission of the external tendon strain to the cytoskeleton.…”