Contractile Equilibration of Single Cells to Step Changes in Extracellular Stiffness

Crow, Ailey; Webster, Kevin D.; Hohlfeld, Evan; Ng, Win Pin; Geissler, Phillip L.; Fletcher, Daniel A.

doi:10.1016/j.bpj.2011.11.4020

Cited by 31 publications

(42 citation statements)

References 45 publications

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“…In ref. 16, an overshoot of the rate adaptation, which relaxed to a long-term rate within 10 s, was noted in addition to the initial instantaneous change of slope. Although this instantaneity at the cell scale is not explained by mechanochemical regulation, this behavior is fully accounted for by the mechanical model proposed here (Fig.…”

Section: Resultsmentioning

confidence: 95%

See 1 more Smart Citation

Cells as liquid motors: Mechanosensitivity emerges from collective dynamics of actomyosin cortex

Etienne

Fouchard

Mitrossilis

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

116

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Living cells adapt and respond actively to the mechanical properties of their environment. In addition to biochemical mechanotransduction, evidence exists for a myosin-dependent purely mechanical sensitivity to the stiffness of the surroundings at the scale of the whole cell. Using a minimal model of the dynamics of actomyosin cortex, we show that the interplay of myosin power strokes with the rapidly remodeling actin network results in a regulation of force and cell shape that adapts to the stiffness of the environment. Instantaneous changes of the environment stiffness are found to trigger an intrinsic mechanical response of the actomyosin cortex. Cortical retrograde flow resulting from actin polymerization at the edges is shown to be modulated by the stress resulting from myosin contractility, which in turn, regulates the cell length in a forcedependent manner. The model describes the maximum force that cells can exert and the maximum speed at which they can contract, which are measured experimentally. These limiting cases are found to be associated with energy dissipation phenomena, which are of the same nature as those taking place during the contraction of a whole muscle. This similarity explains the fact that single nonmuscle cell and wholemuscle contraction both follow a Hill-like force-velocity relationship. -5). This behavior is strongly dependent on the contractile activity of the actomyosin network (6-10). One of the cues driving the cell response to its environment is rigidity (11). Cells are able to sense not only the local rigidity of the material with which they are in contact (12) but also, the one associated with distant cell substrate contacts. This ability has been demonstrated by tracking the amount of extra force needed to achieve a given displacement of microplates between which the cell is placed (13, 14) (Fig. 1B), of an atomic force microscope (AFM) cantilever (15, 16) or elastic micropillars (17). This cell-scale rigidity sensing is totally dependent on myosin-II activity (13). A working model of the molecular mechanisms at play in the actomyosin cortex is available (18), where myosin contraction, actin treadmilling, and actin cross-linker turnover are the main ingredients. Phenomenological models (19, 20) of mechanosensing have been proposed but could not bridge the gap between the molecular microstructure and this cell-scale phenomenology. Here, we show that the collective dynamics of actin, actin cross-linkers, and myosin molecular motors are sufficient to explain cellscale rigidity sensing: depending on the tension that can be borne by the environment, there is a change of the fraction of myosin molecules which perform mechanical work that is effectively transmitted rather than dissipated. The model derivation is analogous to the one of rubber elasticity of transiently cross-linked networks (21), with the addition of active crosslinkers accounting for the myosin. It involves four parameters only: myosin contractile stress, speed of actin treadmilling, elastic modulus, and viscoela...

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Section: Resultsmentioning

confidence: 95%

“…This ability has been demonstrated by tracking the amount of extra force needed to achieve a given displacement of microplates between which the cell is placed (13,14) (Fig. 1B), of an atomic force microscope (AFM) cantilever (15,16) or elastic micropillars (17). This cell-scale rigidity sensing is totally dependent on myosin-II activity (13).…”

mentioning

confidence: 97%

Cells as liquid motors: Mechanosensitivity emerges from collective dynamics of actomyosin cortex

Etienne

Fouchard

Mitrossilis

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

116

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“…[15] Critically, how cells sense and respond to the mechanical properties of their surroundings in a heterogeneous environment and the role of mechanical heterogeneity in mediating skeletal stem cell function remains poorly understood. [4,16] Elastomeric substrates and hydrogels have been used to present cells with surfaces of specific stiffness, approximating the range of rigidities encountered in physiological Environments. [7] Critically, substrates possessing bulk rigidity of circa 20-50 kPa have been previously shown to induce stem cell differentiation to cartilage and bone specific lineages in vitro.…”

Section: Introductionmentioning

confidence: 99%

The Functional Response of Mesenchymal Stem Cells to Electron‐Beam Patterned Elastomeric Surfaces Presenting Micrometer to Nanoscale Heterogeneous Rigidity

et al. 2017

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Biggs, M. J. P. et al. (2017) The functional response of mesenchymal stem cells to electron-beam patterned elastomeric surfaces presenting micrometer to nanoscale heterogeneous rigidity. Advanced Materials, 29(39), 1702119.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.Biggs, M. J.P. et al. (2017) AbstractCells directly probe and respond to the physicomechanical properties of their extracellular environment, a dynamic process which has been shown to play a key role in regulating both cellular adhesive processes and differential cellular function. Recent studies indicate that stem cells show lineage-specific differentiation when cultured on substrates approximating the stiffness profiles of specific tissues. Although tissues are associated with ranging Young's modulus values for bulk rigidity, at the sub-cellular level, and particularly at the micro-and nanoscales, tissues are comprised of heterogeneous distributions of rigidity.Lithographic processes have been widely explored in cell biology for the generation of analytical substrates to probe cellular physicomechanical responses. In this work, we show for the first time that that direct-write e-beam exposure can significantly alter the rigidity of elastomeric PDMS substrates and develop a new class of two-dimensional elastomeric substrates with controlled patterned rigidity ranging from the micron to the nanoscale. The mechano-response of human mesenchymal stem cells to e-beam patterned substrates was subsequently probed in vitro and significant modulation of focal adhesion formation and osteochondral lineage commitment was observed as a function of both feature diameter and rigidity, establishing the groundwork for a new generation of biomimetic material interfaces.3

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“…In fact, recently, several authors carried out this experiment, concluding that contracting cells are able to adapt to the stiffness step change on a short timescale of 10’s of seconds, showing practically an instantaneous response (Crow et al 2012; Mitrossilis et al 2010). …”

Section: Introductionmentioning

confidence: 99%

“…Deshpande et al combined mechanics with time-dependent chemical signaling (Deshpande et al 2006) in order to predict the role of focal adhesions and stress fiber concentration in the development of force by cells. Finally, Crow and co-workers (Crow et al 2012) proposed a three-spring model including a dashpot and an independent actuator contracting at a constant velocity (Fig. 1d), although their approach was focused on capturing the instantaneous cell response rather than the long term behavior.…”

Section: Introductionmentioning

confidence: 99%

A time-dependent phenomenological model for cell mechano-sensing

Borau

Kamm

García-Aznar

2013

Biomech Model Mechanobiol

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Adherent cells normally apply forces as a generic means of sensing and responding to the mechanical nature of their surrounding environment. How these forces vary as a function of the extracellular rigidity is critical to understanding the regulatory functions that drive important phenomena such as wound healing or muscle contraction. In recognition of this fact, experiments have been conducted to understand cell rigidity-sensing properties under known conditions of the extracellular environment, opening new possibilities for modeling this active behaviour. In this work, we provide a physics-based constitutive model taking into account the main structural components of the cell to reproduce its most significant contractile properties such as the traction forces exerted as a function of time and the extracellular stiffness. This model shows how the interplay between the time-dependent response of the acto-myosin contractile system and the elastic response of the cell components determine the mechano-sensing behaviour of single cells.

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Contractile Equilibration of Single Cells to Step Changes in Extracellular Stiffness

Cited by 31 publications

References 45 publications

Cells as liquid motors: Mechanosensitivity emerges from collective dynamics of actomyosin cortex

Cells as liquid motors: Mechanosensitivity emerges from collective dynamics of actomyosin cortex

The Functional Response of Mesenchymal Stem Cells to Electron‐Beam Patterned Elastomeric Surfaces Presenting Micrometer to Nanoscale Heterogeneous Rigidity

A time-dependent phenomenological model for cell mechano-sensing

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