Limits...
Matrix viscoplasticity and its shielding by active mechanics in microtissue models: experiments and mathematical modeling

View Article: PubMed Central - PubMed

ABSTRACT

The biomechanical behavior of tissues under mechanical stimulation is critically important to physiological function. We report a combined experimental and modeling study of bioengineered 3D smooth muscle microtissues that reveals a previously unappreciated interaction between active cell mechanics and the viscoplastic properties of the extracellular matrix. The microtissues’ response to stretch/unstretch actuations, as probed by microcantilever force sensors, was dominated by cellular actomyosin dynamics. However, cell lysis revealed a viscoplastic response of the underlying model collagen/fibrin matrix. A model coupling Hill-type actomyosin dynamics with a plastic perfectly viscoplastic description of the matrix quantitatively accounts for the microtissue dynamics, including notably the cells’ shielding of the matrix plasticity. Stretch measurements of single cells confirmed the active cell dynamics, and were well described by a single-cell version of our model. These results reveal the need for new focus on matrix plasticity and its interactions with active cell mechanics in describing tissue dynamics.

No MeSH data available.


Related in: MedlinePlus

Dynamic response of microtissues to stretch.Shown are the stretch/unstretch responses of an untreated control (Tissue C1) and a Triton X-100 treated microtissue (Tissue T1) to magnetic forcing. (a) Magnetic force profile FMag vs time t applied via Ni sphere to control microtissue. (b) Resulting incremental strain δε vs t and (c) incremental stress δσ vs t profiles measured relative to the as-grown tissue configuration, which had a baseline stress σ0 = 6.66 kPa. (d) Incremental stress-strain curve δσ vs δε. (e–h) Corresponding results for the Triton-treated microtissue, with δε and δσ measured relative to the configuration following treatment where σ0 = 1.56 kPa. The control tissue’s response is characterized by an active recovery to close to its initial state while the Triton-treated tissue shows irreversible plastic deformation. The blue curves in (c,d) are the result of a fit to the model shown in Fig. 3. The red and green traces in (c) show the cell and ECM contributions to the incremental stress, δσa and δσp, respectively, as determined from the model. The green curves in (g,h) are a fit including ECM contributions of the model only. The parameters for these fits are given in Supplementary Table 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5037370&req=5

f2: Dynamic response of microtissues to stretch.Shown are the stretch/unstretch responses of an untreated control (Tissue C1) and a Triton X-100 treated microtissue (Tissue T1) to magnetic forcing. (a) Magnetic force profile FMag vs time t applied via Ni sphere to control microtissue. (b) Resulting incremental strain δε vs t and (c) incremental stress δσ vs t profiles measured relative to the as-grown tissue configuration, which had a baseline stress σ0 = 6.66 kPa. (d) Incremental stress-strain curve δσ vs δε. (e–h) Corresponding results for the Triton-treated microtissue, with δε and δσ measured relative to the configuration following treatment where σ0 = 1.56 kPa. The control tissue’s response is characterized by an active recovery to close to its initial state while the Triton-treated tissue shows irreversible plastic deformation. The blue curves in (c,d) are the result of a fit to the model shown in Fig. 3. The red and green traces in (c) show the cell and ECM contributions to the incremental stress, δσa and δσp, respectively, as determined from the model. The green curves in (g,h) are a fit including ECM contributions of the model only. The parameters for these fits are given in Supplementary Table 1.

Mentions: Mechanical forces were applied to the microtissues via magnetic forces produced on the nickel spheres by the pole tip of an electromagnetic tweezer, as shown in Fig. 1b,d. We applied a stretch-unstretch protocol in which the magnetic force FMag was increased to 25–35 μN over 120 s, and then decreased to zero over a similar time interval, as shown in Fig. 2a. The deflections of the pillars caused by FMag and the motion of the microtissues under test were recorded by time-lapse phase contrast and fluorescence microscopy during force application, and for a 15 min interval after the cessation of the applied force. Figure 2b shows the time evolution of the incremental strain δε = ε − ε0 of a microtissue in response to FMag, where ε is the absolute strain and ε0 is the baseline strain before FMag is applied. Figure 2c depicts the corresponding incremental stress δσ = σ − σ0, where σ is the absolute stress, and σ0 is the baseline stress.


Matrix viscoplasticity and its shielding by active mechanics in microtissue models: experiments and mathematical modeling
Dynamic response of microtissues to stretch.Shown are the stretch/unstretch responses of an untreated control (Tissue C1) and a Triton X-100 treated microtissue (Tissue T1) to magnetic forcing. (a) Magnetic force profile FMag vs time t applied via Ni sphere to control microtissue. (b) Resulting incremental strain δε vs t and (c) incremental stress δσ vs t profiles measured relative to the as-grown tissue configuration, which had a baseline stress σ0 = 6.66 kPa. (d) Incremental stress-strain curve δσ vs δε. (e–h) Corresponding results for the Triton-treated microtissue, with δε and δσ measured relative to the configuration following treatment where σ0 = 1.56 kPa. The control tissue’s response is characterized by an active recovery to close to its initial state while the Triton-treated tissue shows irreversible plastic deformation. The blue curves in (c,d) are the result of a fit to the model shown in Fig. 3. The red and green traces in (c) show the cell and ECM contributions to the incremental stress, δσa and δσp, respectively, as determined from the model. The green curves in (g,h) are a fit including ECM contributions of the model only. The parameters for these fits are given in Supplementary Table 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037370&req=5

f2: Dynamic response of microtissues to stretch.Shown are the stretch/unstretch responses of an untreated control (Tissue C1) and a Triton X-100 treated microtissue (Tissue T1) to magnetic forcing. (a) Magnetic force profile FMag vs time t applied via Ni sphere to control microtissue. (b) Resulting incremental strain δε vs t and (c) incremental stress δσ vs t profiles measured relative to the as-grown tissue configuration, which had a baseline stress σ0 = 6.66 kPa. (d) Incremental stress-strain curve δσ vs δε. (e–h) Corresponding results for the Triton-treated microtissue, with δε and δσ measured relative to the configuration following treatment where σ0 = 1.56 kPa. The control tissue’s response is characterized by an active recovery to close to its initial state while the Triton-treated tissue shows irreversible plastic deformation. The blue curves in (c,d) are the result of a fit to the model shown in Fig. 3. The red and green traces in (c) show the cell and ECM contributions to the incremental stress, δσa and δσp, respectively, as determined from the model. The green curves in (g,h) are a fit including ECM contributions of the model only. The parameters for these fits are given in Supplementary Table 1.
Mentions: Mechanical forces were applied to the microtissues via magnetic forces produced on the nickel spheres by the pole tip of an electromagnetic tweezer, as shown in Fig. 1b,d. We applied a stretch-unstretch protocol in which the magnetic force FMag was increased to 25–35 μN over 120 s, and then decreased to zero over a similar time interval, as shown in Fig. 2a. The deflections of the pillars caused by FMag and the motion of the microtissues under test were recorded by time-lapse phase contrast and fluorescence microscopy during force application, and for a 15 min interval after the cessation of the applied force. Figure 2b shows the time evolution of the incremental strain δε = ε − ε0 of a microtissue in response to FMag, where ε is the absolute strain and ε0 is the baseline strain before FMag is applied. Figure 2c depicts the corresponding incremental stress δσ = σ − σ0, where σ is the absolute stress, and σ0 is the baseline stress.

View Article: PubMed Central - PubMed

ABSTRACT

The biomechanical behavior of tissues under mechanical stimulation is critically important to physiological function. We report a combined experimental and modeling study of bioengineered 3D smooth muscle microtissues that reveals a previously unappreciated interaction between active cell mechanics and the viscoplastic properties of the extracellular matrix. The microtissues’ response to stretch/unstretch actuations, as probed by microcantilever force sensors, was dominated by cellular actomyosin dynamics. However, cell lysis revealed a viscoplastic response of the underlying model collagen/fibrin matrix. A model coupling Hill-type actomyosin dynamics with a plastic perfectly viscoplastic description of the matrix quantitatively accounts for the microtissue dynamics, including notably the cells’ shielding of the matrix plasticity. Stretch measurements of single cells confirmed the active cell dynamics, and were well described by a single-cell version of our model. These results reveal the need for new focus on matrix plasticity and its interactions with active cell mechanics in describing tissue dynamics.

No MeSH data available.


Related in: MedlinePlus