“…Due to the complexity of visualising MA of substrate adhered cells, previous MA studies have focused primarily on cells suspended in media. In particular, suspended endothelial cells [2][3][4], suspended chondrocytes [5][6][7], suspended stem cells [8], and suspended fibroblasts [9] have been tested using the MA technique. However such studies are of limited value as these cell phenotypes are typically not found suspended in vivo; rather, they adhere to an extra cellular matrix.…”
Section: Discussionmentioning
confidence: 99%
“…Previous studies have used simplified passive models analytical [3][4][5]28] or numerical models of passive homogeneous elastic or viscoelastic cells to interpret experimentally observed aspiration curves. Typically such studies report elastic or viscoelastic material parameters based on a curve fit of experimental results.…”
Section: Discussionmentioning
confidence: 99%
“…However, primarily due to the technical complexity of performing MA on cells adhered to a substrate or extra cellular matrix (ECM), the MA technique has largely been limited to the investigation of un-adhered cells suspended in media. Previous experimental MA studies have focused on suspended endothelial cells [2][3][4], suspended chondrocytes [5][6][7], suspended stem cells [8], and suspended fibroblasts [9]. Critically, in suspended cells a fibrillous contractile actin cytoskeleton is not developed [2,10].…”
Publication InformationReynolds, NH,Ronan, W,Dowling, EP,Owens, P,McMeeking, RM,McGarry, JP (2014) 'On the role of the actin cytoskeleton and nucleus in the biomechanical response of spread cells '. Biomaterials,.
“…Due to the complexity of visualising MA of substrate adhered cells, previous MA studies have focused primarily on cells suspended in media. In particular, suspended endothelial cells [2][3][4], suspended chondrocytes [5][6][7], suspended stem cells [8], and suspended fibroblasts [9] have been tested using the MA technique. However such studies are of limited value as these cell phenotypes are typically not found suspended in vivo; rather, they adhere to an extra cellular matrix.…”
Section: Discussionmentioning
confidence: 99%
“…Previous studies have used simplified passive models analytical [3][4][5]28] or numerical models of passive homogeneous elastic or viscoelastic cells to interpret experimentally observed aspiration curves. Typically such studies report elastic or viscoelastic material parameters based on a curve fit of experimental results.…”
Section: Discussionmentioning
confidence: 99%
“…However, primarily due to the technical complexity of performing MA on cells adhered to a substrate or extra cellular matrix (ECM), the MA technique has largely been limited to the investigation of un-adhered cells suspended in media. Previous experimental MA studies have focused on suspended endothelial cells [2][3][4], suspended chondrocytes [5][6][7], suspended stem cells [8], and suspended fibroblasts [9]. Critically, in suspended cells a fibrillous contractile actin cytoskeleton is not developed [2,10].…”
Publication InformationReynolds, NH,Ronan, W,Dowling, EP,Owens, P,McMeeking, RM,McGarry, JP (2014) 'On the role of the actin cytoskeleton and nucleus in the biomechanical response of spread cells '. Biomaterials,.
“…Responses of endothelial cells (ECs) to haemodynamic forces play a significant role in vascular health and disease [4][5][6][7][8][9]. It is well known that ECs transduce the fluid shear stress (FSS) resulting from blood flow into intracellular signals that affect gene expression and cellular functions such as proliferation, apoptosis, migration, permeability, cell alignment and mechanical properties [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The activation of signalling pathways by shear forces arises at discrete locations in ECs by force amplification and forceinduced directional biasing of signal propagation [1][2][3][4][10][11][12][16][17][18][20][21][22][23].…”
Haemodynamic forces applied at the apical surface of vascular endothelial cells (ECs) provide the mechanical signals at intracellular organelles and through the inter-connected cellular network. The objective of this study is to quantify the intracellular and intercellular stresses in a confluent vascular EC monolayer. A novel three-dimensional, multiscale and multicomponent model of focally adhered ECs is developed to account for the role of potential mechanosensors (glycocalyx layer, actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs) and adherens junctions (ADJs)) in mechanotransmission and EC deformation. The overriding issue addressed is the stress amplification in these regions, which may play a role in subcellular localization of mechanotransmission. The model predicts that the stresses are amplified 250-600-fold over apical values at ADJs and 175-200-fold at FAs for ECs exposed to a mean shear stress of 10 dyne cm 22 . Estimates of forces per molecule in the cell attachment points to the external cellular matrix and cell-cell adhesion points are of the order of 8 pN at FAs and as high as 3 pN at ADJs, suggesting that direct force-induced mechanotransmission by single molecules is possible in both. The maximum deformation of an EC in the monolayer is calculated as 400 nm in response to a mean shear stress of 1 Pa applied over the EC surface which is in accord with measurements. The model also predicts that the magnitude of the cell-cell junction inclination angle is independent of the cytoskeleton and glycocalyx. The inclination angle of the cell-cell junction is calculated to be 6.68 in an EC monolayer, which is somewhat below the measured value (9.98) reported previously for ECs subjected to 1.6 Pa shear stress for 30 min. The present model is able, for the first time, to cross the boundaries between different length scales in order to provide a global view of potential locations of mechanotransmission.
“…In turn, wall topography must "two-way couple" to WSS. Phenomenologically, this coupling (of EC morphology with WSS) manifests itself in increasing WSS with changes in EC conformation (6): in vitro, ECs elongate, changing from a polygonal, 'cobblestone' morphology to flattened, elongated ovoids (Figures 2a, 2b), the degree of elongation correlating with the magnitude of the shear stress (7)(8)(9)(10). Note that WSS type, too, is relevant-under oscillatory shear, cultured cells retain a polygonal shape (8) and in vivo, ECs have been shown to orientate to the predominant local flow direction (11), perpendicular to the direction of cyclic stretch (12,13).…”
We discuss, from the perspective of basic science, the physical and biological processes which underlie atherosclerotic (plaque) initiation at the vascular endothelium, identifying the widely separated spatial and temporal scales which participate. We draw on current, related models of vessel wall evolution, paying particular attention to the role of particulate flow (blood is not a -2 -continuum fluid), and proceed to propose, then validate all the key components in a multiplycoupled, multi-scale modeling strategy (in qualitative terms only, note). Eventually, this strategy should lead to a quantitative, patient-specific understanding of the coupling between particulate flow and the endothelial state.
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