Simulation of the Mechanical Response of Cells on Micropost Substrates

Ronan, William; Pathak, Amit; Deshpande, V.S.; McMeeking, Robert M.; McGarry, J. Patrick

doi:10.1115/1.4025114

Cited by 14 publications

(15 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taken together, these results demonstrate that the bio-chemo-mechanical model can capture general characteristics of cellular contractility observed in previous experiments [132,144,157,180]. More recently, cellular mechanotransduction response simulation conducted by Ronan et al [127] also found that higher level of stress fiber assembly most concentrates on cell periphery, especially around the peripheral post adhesion sites, which provides rational interpretation for experimental results that individual force measured by micropost deflection increases linearly from cell center to periphery. As depicted in Fig.…”

Section: Simulations Of Cellular Contractility On Micropost Substratessupporting

confidence: 68%

“…A novel approach combined optical tracking technique with micropost force sensor arrays was proposed to quantify twitch power, and an intriguing phenomenon was found that [157], and the red box represents the predicted results [127]. The shaded region (blue) depicts the area of focal adhesions smaller than 1 µm 2 (color figure online) neonatal cardiomyocytes possess larger twitch power and lower twitch velocities with stiffer substrates [126], which attributes in part to cells on rigid substrate that can form reinforced myofibril structure and possess increased calcium levels.…”

Section: Effects Of Micropost Stiffness On Cellular Contractilitymentioning

confidence: 98%

“…The active integrins form bond and interact with underlying substrates; therefore, the potential energy in bond and the additional energy from stretching contribute to the chemical potential of high-affinity integrins, χ H , at concentration ξ H [11,40,114], where Φ(∆ i ) is stretching energy and F i ∆ i is consuming mechanical energy under the action of stretching force F i during bond stretching ∆ i . And the stretching force is determined by Birchenall and Shemesh et al [11,141], The concentrations of low-and high-affinity integrins are determined through assuming thermodynamic equilibrium of two integrins' concentration (χ L = χ H ) and ignoring diffusive fluxes [40,127], The stretching energy is obtained by a simple piecewise quadratic potential [40], where s is the bond stiffness, ∆ n is the maximum length of bonds, and ∆ e = ∆ 2 1 + ∆ 2 2 denotes the effective stretching magnitude. The traction force, which is balanced with contractile force generated by stress fibers, is determined by the stretching force F i and active integrin concentration ξ H [40,127], (6) …”

Section: Focal Adhesion Modelmentioning

confidence: 99%

“…And the stretching force is determined by Birchenall and Shemesh et al [11,141], The concentrations of low-and high-affinity integrins are determined through assuming thermodynamic equilibrium of two integrins' concentration (χ L = χ H ) and ignoring diffusive fluxes [40,127], The stretching energy is obtained by a simple piecewise quadratic potential [40], where s is the bond stiffness, ∆ n is the maximum length of bonds, and ∆ e = ∆ 2 1 + ∆ 2 2 denotes the effective stretching magnitude. The traction force, which is balanced with contractile force generated by stress fibers, is determined by the stretching force F i and active integrin concentration ξ H [40,127], (6) …”

Section: Focal Adhesion Modelmentioning

confidence: 99%

See 3 more Smart Citations

Review of cellular mechanotransduction on micropost substrates

Geng

Wang

2015

Med Biol Eng Comput

View full text Add to dashboard Cite

As physical entities, living cells can sense and respond to various stimulations within and outside the body through cellular mechanotransduction. Any deviation in cellular mechanotransduction will not only undermine the orchestrated regulation of mechanical responses, but also lead to the breakdown of their physiological function. Therefore, a quantitative study of cellular mechanotransduction needs to be conducted both in experiments and in computational simulations to investigate the underlying mechanisms of cellular mechanotransduction. In this review, we present an overview of the current knowledge and significant progress in cellular mechanotransduction via micropost substrates. In the aspect of experimental studies, we summarize significant experimental progress and place an emphasis on the coupled relationship among cellular spreading, focal adhesion and contractility as well as the influence of substrate properties on force-involved cellular behaviors. In the other aspect of computational investigations, we outline a coupled framework including the biochemically motivated stress fiber model and thermodynamically motivated adhesion model and present their predicted biomechanical responses and then compare predicted simulation results with experimental observations to further explore the mechanisms of cellular mechanotransduction. At last, we discuss the future perspectives both in experimental technologies and in computational models, as well as facing challenges in the area of cellular mechanotransduction.

show abstract

Section: Simulations Of Cellular Contractility On Micropost Substratessupporting

confidence: 68%

Section: Effects Of Micropost Stiffness On Cellular Contractilitymentioning

confidence: 98%

Section: Focal Adhesion Modelmentioning

confidence: 99%

Section: Focal Adhesion Modelmentioning

confidence: 99%

See 2 more Smart Citations

Review of cellular mechanotransduction on micropost substrates

Geng

Wang

2015

Med Biol Eng Comput

View full text Add to dashboard Cite

show abstract

“…This leads to tension dependent FA formation, whereby increasing traction increases the concentration of bound integrins and, consequently, the stiffness of the adhesion. We note in passing that FA distributions have been previously studied by the authors (Pathak et al, 2008;Ronan et al, 2013) and, hence, we do not present details of FA distributions in the current study.…”

Section: Modelling Approachmentioning

confidence: 86%

Cooperative contractility: The role of stress fibres in the regulation of cell-cell junctions

Ronan

McMeeking

Chen

et al. 2015

Journal of Biomechanics

Self Cite

View full text Add to dashboard Cite

We present simulations of cell-cell adhesion as reported in a recent study [Liu et al., 2010, PNAS, 107(22), 9944-9] for two cells seeded on an array of micro-posts. The micro-post array allows for the measurement of forces exerted by the cell and these show that the cell-cell tugging stress is a constant and independent of the cell-cell junction area. In the current study, we demonstrate that a material model which includes the underlying cellular processes of stress fibre contractility and adhesion formation can capture these results. The simulations explain the experimentally observed phenomena whereby the cell-cell junction forces increase with junction size but the tractions exerted by the cell on the micro-post array are independent of the junction size. Further simulations on different types of micro-post arrays and cell phenotypes are presented as a guide to future experiments.3

show abstract

Bio-chemo-mechanical models for nuclear deformation in adherent eukaryotic cells

Nava

Raimondi

Pietrabissa

2014

Biomech Model Mechanobiol

View full text Add to dashboard Cite

Adherent eukaryotic cells are subjected to a broad variety of extracellular and intracellular stimuli regulating their behaviour. These stimuli can be either purely chemical, for example soluble factors binding to the cell membrane, or mechano-chemical, for example integrin-based adhesion complexes stretching the cell cytoskeleton. Here, we focus on mechano-chemical stimuli such as extracellular forces (interstitial flow, pressurization) and intracellular forces (due to cell adhesion), which may combine generating stress-strain states in the cytoskeleton. These states are transferred to the nucleus to influence the transcription of specific genes, likely by changing the chromatin organization and by altering the permeability of the nuclear membrane. While there exists increasing experimental evidence of the mechanosensing role of the cell nucleus, both the underlying molecular mechanisms involved, and the nuclear structural behaviour in response to forces, are still poorly understood. Here, we review the existing literature on computational models developed to investigate the chemo-mechanical behaviour of adherent eukaryotic cells. We analyse two main classes of models of single-cell mechanics, based either on the discrete or on the continuum approaches. We focus on the bio-chemo-mechanical model and modelling techniques accounting for the nuclear body. The modelling techniques are discussed highlighting their ability in predicting cytoskeletal contractility states and nuclear stress-strain states.

show abstract

Simulation of the Mechanical Response of Cells on Micropost Substrates

Cited by 14 publications

References 37 publications

Review of cellular mechanotransduction on micropost substrates

Review of cellular mechanotransduction on micropost substrates

Cooperative contractility: The role of stress fibres in the regulation of cell-cell junctions

Bio-chemo-mechanical models for nuclear deformation in adherent eukaryotic cells

Contact Info

Product

Resources

About