A thermodynamically motivated model for stress-fiber reorganization

Vigliotti, Andrea; Ronan, William; Baaijens, Fpt Frank; Deshpande, V.S.

doi:10.1007/s10237-015-0722-9

Cited by 56 publications

(97 citation statements)

References 40 publications

(72 reference statements)

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“…The implementation of the homeostatic mechanics approach described above requires a specific model for the mechano-bio-chemistry of stress-fibres and focal adhesions [26][27][28].…”

Section: Homeostatic Mechanics Predictions Reproduce Morphometric Obsmentioning

confidence: 99%

Entropic forces drive cellular contact guidance

Buskermolen

Suresh²,

Shishvan

et al. 2018

Preprint

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Contact guidance-the widely-known phenomenon of cell alignment induced by anisotropic environmental features-is an essential step in the organization of adherent cells, but the mechanisms by which cells achieve this orientational ordering remain unclear. Here we seeded myofibroblasts on substrates micropatterned with stripes of fibronectin and observed that contact guidance emerges at stripe widths much greater than the cell size. To understand the origins of this surprising observation, we combined morphometric analysis of cells and their subcellular components with a novel statistical framework for modelling non-thermal fluctuations of living cells. This modelling framework is shown to predict not only the trends but also the statistical variability of a wide range of biological observables including cell (and nucleus) shapes, sizes and orientations, as well as stress-fibre arrangements within the cells with remarkable fidelity. By comparing observations and theory, we identified two regimes of contact guidance: (i) guidance on stripe widths smaller than the cell size ( ≤ 160 μm), which is accompanied by biochemical changes within the cells, including increasing stress-fibre polarisation and cell elongation, and (ii) entropic guidance on larger stripe widths, which is governed by fluctuations in the cell morphology. Overall, our findings suggest an entropymediated mechanism for contact guidance associated with the tendency of cells to maximise their morphological entropy through shape fluctuations.

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“…The implementation of the homeostatic mechanics approach described above requires a specific model for the mechano-bio-chemistry of stress-fibres and focal adhesions [26][27][28].…”

Section: Homeostatic Mechanics Predictions Reproduce Morphometric Obsmentioning

confidence: 99%

Entropic forces drive cellular contact guidance

Buskermolen

Suresh²,

Shishvan

et al. 2018

Preprint

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“…Here we are interested in investigating the differentiation behaviour of hMSCs to mechanical cues provided by the substrate stiffness [6] and geometric cues imposed by the size of adhesive islands patterned on substrates [3]. These cues are known to result in significant remodelling of the stress-fibre cytoskeleton and thus here we use a model for the Gibbs free-energy developed by Vigliotti et al [31] and subsequently modified in [26][27][28]. Details of the model including the parameters are given in Supplementary S1.3 and here we give a brief overview.…”

Section: Gibbs Free-energy Of a Morphological Microstatementioning

confidence: 99%

“…Unlike, deterministic free-energy models [31][32][33] that treat cells as systems that minimise their free-energy, the homeostatic ensemble recognises that cells exchange nutrients with their environment and thereby maintain a thermodynamic non-equilibrium but nevertheless stationary state that is commonly referred to as the homeostatic state. In this homeostatic state, hMSCs fluctuate over the equilibrium distribution of morphological microstates characterised by (1) and thus have a fluctuating ̂c yto .…”

Section: Early Forecasting Of the Lineage Of Hmscsmentioning

confidence: 99%

Free-energy-based framework for early forecasting of stem cell differentiation

Suresh¹,

Shishvan²,

Vigliotti

et al. 2019

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Commitment of stem cells to different lineages is inherently stochastic but regulated by a range of environmental bio/chemo/mechanical cues. Here we develop an integrated stochastic modelling framework for predicting the differentiation of hMSCs in response to a range of environmental cues including sizes of adhesive islands, stiffness of substrates and treatment with ROCK inhibitors in both growth and mixed media. The statistical framework analyses the fluctuations of cell morphologies over around a 24-hour period after seeding the cells in the specific environment and uses the distribution of their cytoskeletal free-energy to forecast the lineage the hMSCs will commit to. The cytoskeletal free-energy which succinctly parameterises the biochemical state of the cell is shown to capture hMSC commitment over a range of environments while simple morphological factors such as cell shape, tractions on their own are unable to correlate with lineages hMSCs adopt.

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“…An improved knowledge of this process is of key importance to understand the functioning of human tissues, during both health and disease. To date, it remains unknown what mechanical quantity determines tissue homeostasis; in fact, different measures have been associated to play important roles in this process, such as stress [4,5], strain [6,7], strain rate [6,8] and strain energy [8]. Moreover, mechanical homeostasis is not necessarily determined by the same mechanical parameters across different tissue types.…”

Section: Introductionmentioning

confidence: 99%