scholarly journals A feedback-loop extended stress fiber growth model with focal adhesion formation

2017 ◽  
Vol 128 ◽  
pp. 160-173 ◽  
Author(s):  
Pradeep Keshavanarayana ◽  
Martin Ruess ◽  
René de Borst
Keyword(s):  
Growth Model ◽  
Focal Adhesion ◽  
Feedback Loop ◽  
Adhesion Formation ◽  
Stress Fiber ◽  
Fiber Growth ◽  
Focal Adhesion Formation

An Analysis of the Cooperative Mechano-Sensitive Feedback Between Intracellular Signaling, Focal Adhesion Development, and Stress Fiber Contractility

2011 ◽  
Vol 78 (4) ◽  
Author(s):  
Amit Pathak ◽  
Robert M. McMeeking ◽  
Anthony G. Evans ◽  
Vikram S. Deshpande
Keyword(s):  
Mechanical Loading ◽  
Focal Adhesion ◽  
Intracellular Signaling ◽  
Feedback Loop ◽  
Adhesion Formation ◽  
Focal Adhesions ◽  
Stress Fiber ◽  
Mechanical Loads ◽  
Signaling Model ◽  
Wide Range

Cells communicate with their external environment via focal adhesions and generate activation signals that in turn trigger the activity of the intracellular contractile machinery. These signals can be triggered by mechanical loading that gives rise to a cooperative feedback loop among signaling, focal adhesion formation, and cytoskeletal contractility, which in turn equilibrates with the applied mechanical loads. We devise a signaling model that couples stress fiber contractility and mechano-sensitive focal adhesion models to complete this above mentioned feedback loop. The signaling model is based on a biochemical pathway where IP3 molecules are generated when focal adhesions grow. These IP3 molecules diffuse through the cytosol leading to the opening of ion channels that disgorge Ca2+ from the endoplasmic reticulum leading to the activation of the actin/myosin contractile machinery. A simple numerical example is presented where a one-dimensional cell adhered to a rigid substrate is pulled at one end, and the evolution of the stress fiber activation signal, stress fiber concentrations, and focal adhesion distributions are investigated. We demonstrate that while it is sufficient to approximate the activation signal as spatially uniform due to the rapid diffusion of the IP3 through the cytosol, the level of the activation signal is sensitive to the rate of application of the mechanical loads. This suggests that ad hoc signaling models may not be able to capture the mechanical response of cells to a wide range of mechanical loading events.

Simulation of the Mechanical Response of Cells on Micropost Substrates

2013 ◽  
Vol 135 (10) ◽  
Author(s):  
William Ronan ◽  
Amit Pathak ◽  
Vikram S. Deshpande ◽  
Robert M. McMeeking ◽  
J. Patrick McGarry
Keyword(s):  
Focal Adhesion ◽  
Computational Models ◽  
Mechanical Response ◽  
Adhesion Formation ◽  
Experimental Studies ◽  
Stress Fiber ◽  
Cell Behavior ◽  
Rate Dependent ◽  
Focal Adhesion Formation ◽  
Biomechanical Response

Experimental studies where cells are seeded on micropost arrays in order to quantify their contractile behavior are becoming increasingly common. Interpretation of the data generated by this experimental technique is difficult, due to the complexity of the processes underlying cellular contractility and mechanotransduction. In the current study, a coupled framework that considers strain rate dependent contractility and remodeling of the cytoskeleton is used in tandem with a thermodynamic model of tension dependent focal adhesion formation to investigate the biomechanical response of cells adhered to micropost arrays. Computational investigations of the following experimental studies are presented: cell behavior on different sized arrays with a range of post stiffness; stress fiber and focal adhesion formation in irregularly shaped cells; the response of cells to deformations applied locally to individual posts; and the response of cells to equibiaxial stretching of micropost arrays. The predicted stress fiber and focal adhesion distributions; in addition to the predicted post tractions are quantitatively and qualitatively supported by previously published experimental data. The computational models presented in this study thus provide a framework for the design and interpretation of experimental micropost studies.

Simulation of the Coupling of Cell Contractility and Focal Adhesion Formation

2007 ◽  
Author(s):  
Amit Pathak ◽  
Vikram S. Deshpande ◽  
Robert M. McMeeking ◽  
Anthony G. Evans
Keyword(s):  
Focal Adhesion ◽  
Adhesion Formation ◽  
High Stress ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Stress Fibers ◽  
Cell Contractility ◽  
Focal Adhesion Formation ◽  
Pattern Shape ◽  
Stress Dependent

The remodeling of the cytoskeleton and focal adhesion distributions for cells on substrates with micro-patterned ligand patches is investigated using a bio-chemo-mechanical model. All the cells have approximately the same area and we investigate the effect of ligand pattern shape on the cytoskeletal arrangements and focal adhesion distributions. The model for the cytoskeleton accounts for the dynamic rearrangement of the actin/myosin stress fibers and entails the highly non-linear interactions between signaling, the kinetics of tension-dependent stress-fiber formation/dissolution and stress dependent contractility. This model is coupled with a focal adhesion (FA) model that accounts for the mechano-sensitivity of the adhesions from thermodynamic considerations. This coupled stress fiber and focal adhesion model is shown to capture a variety of key experimental observations including: (i) the formation of high stress fiber and focal adhesion concentrations at the periphery of circular and triangular, convex–shaped ligand patterns; (ii) the development of high focal adhesion concentrations along the edges of the V, T, Y and U shaped concave ligand patterns; and (iii) the formation of highly aligned stress fibers along the un-adhered edges of cells on the concave ligand patterns. When appropriately calibrated, the model also accurately predicts the radii of curvature of the un-adhered edges of cells on the concave-shaped ligand patterns.

Abstract 110: Thrombospondin Type-1 Domain-Containing Protein 1 (THSD1), an Intracranial Aneurysm Susceptibility Gene, Mediates Cell Adhesion in Human Umbilical Vein Endothelial Cells

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Xiaoqian Fang ◽  
Dong H Kim ◽  
Teresa Santiago-Sim
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Focal Adhesion ◽  
Umbilical Vein ◽  
Adhesion Formation ◽  
Wild Type ◽  
Focal Adhesion Formation ◽  
Umbilical Vein Endothelial Cells

Introduction: An intracranial aneurysm (IA) is a weak spot in cerebral blood vessel wall that can lead to its abnormal bulging. Previously, we reported that mutations in THSD1 , encoding thrombospondin type-1 domain-containing protein 1, are associated with IA in a subset of patients. THSD1 is a transmembrane molecule with a thrombospondin type-1 repeat (TSR). Proteins with TSR domain have been implicated in a variety of processes including regulation of matrix organization, cell adhesion and migration. We have shown that in mouse brain Thsd1 is expressed in endothelial cells. Hypothesis: THSD1 plays an important role in maintaining the integrity of the endothelium by promoting adhesion of endothelial cells to the underlying basement membrane. Methods: Human umbilical vein endothelial cells are used to investigate the role of THSD1 in vitro . THSD1 expression was knocked-down by RNA interference. Cell adhesion assay was done on collagen I-coated plates and focal adhesion formation was visualized using immunofluorescence by paxillin and phosphorylated focal adhesion kinase (pFAK) staining. THSD1 re-expression is accomplished by transfection with a pCR3.1-THSD1-encoding plasmid. Results: Knockdown of THSD1 caused striking change in cell morphology and size. Compared to control siRNA-treated cells that exhibited typical cobblestone morphology, THSD1 knockdown cells were narrow and elongated, and were significantly smaller ( p <0.01). Cell adherence to collagen I-coated plates was also attenuated in THSD1 knockdown cells ( p <0.01). Consistent with this finding is the observation that the number and size of focal adhesions, based on paxillin and pFAK staining, were significantly reduced after THSD1 knockdown ( p <0.01). These defects in cell adhesion and focal adhesion formation were rescued by re-expression of wild type THSD1 ( p <0.05). In contrast, initial studies indicate that expression of mutated versions of THSD1 as seen in human patients (L5F, R450*, E466G, P639L) could not restore cell adhesion and focal adhesion formation to wild type levels. Conclusions: Our studies provide evidence for a role of THSD1 and THSD1 mutations in endothelial cell adhesion and suggest a possible mechanism underlying THSD1 -mediated aneurysm disease.

Nanoporosity Stimulates Cell Spreading and Focal Adhesion Formation in Cells with Mutated Paxillin

2020 ◽  
Vol 12 (13) ◽  
pp. 14924-14932
Author(s):  
Dainelys Guadarrama Bello ◽  
Aurélien Fouillen ◽  
Antonella Badia ◽  
Antonio Nanci
Keyword(s):  
Focal Adhesion ◽  
Adhesion Formation ◽  
Cell Spreading ◽  
Focal Adhesion Formation ◽  
In Cells
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