Abstract:The cardiac milieu is mechanically active with spontaneous contraction beginning from early development and persistent through maturation and homeostasis, suggesting that mechanical loading may provide biomimetic myocardial developmental signal. In this study, we tested the role of cyclic mechanical stretch loading in the cardiomyogenesis of pluripotent murine embryonic (P19) stem cells. A Flexcell tension system was utilized to apply equiaxial stretch (12% strain, 1.25 Hz frequency) to P19 cell-derived embryo… Show more
“…This allows the method to be adapted to each study based on the anticipated displacements and available imaging resolution. BPM, calculated by the fast Fourier transform (FFT) of the displacement signal and verified with an automated peak counter, was 75.0 for the beating areas having displacement more than 0.14 μm; which is comparable to BPMs in previous studies including ours 2,14,15 .Figure 2In AR-DIC of beating CMs, accurate displacement measurement and combined sarcomere length-based physiological contraction criteria provide multiple quantitative biomechanics data critical for assessing functional myocardial tissue development. Displacement at a time frame showing the maximum displacement for contracting ( A ) and non-contracting ( B ) samples, respectively.…”
We developed an Adaptive Reference-Digital Image Correlation (AR-DIC) method that enables unbiased and accurate mechanics measurements of moving biological tissue samples. We applied the AR-DIC analysis to a spontaneously beating cardiomyocyte (CM) tissue, and could provide correct quantifications of tissue displacement and strain for the beating CMs utilizing physiologically-relevant, sarcomere displacement length-based contraction criteria. The data were further synthesized into novel spatiotemporal parameters of CM contraction to account for the CM beating homogeneity, synchronicity, and propagation as holistic measures of functional myocardial tissue development. Our AR-DIC analyses may thus provide advanced non-invasive characterization tools for assessing the development of spontaneously contracting CMs, suggesting an applicability in myocardial regenerative medicine.
“…This allows the method to be adapted to each study based on the anticipated displacements and available imaging resolution. BPM, calculated by the fast Fourier transform (FFT) of the displacement signal and verified with an automated peak counter, was 75.0 for the beating areas having displacement more than 0.14 μm; which is comparable to BPMs in previous studies including ours 2,14,15 .Figure 2In AR-DIC of beating CMs, accurate displacement measurement and combined sarcomere length-based physiological contraction criteria provide multiple quantitative biomechanics data critical for assessing functional myocardial tissue development. Displacement at a time frame showing the maximum displacement for contracting ( A ) and non-contracting ( B ) samples, respectively.…”
We developed an Adaptive Reference-Digital Image Correlation (AR-DIC) method that enables unbiased and accurate mechanics measurements of moving biological tissue samples. We applied the AR-DIC analysis to a spontaneously beating cardiomyocyte (CM) tissue, and could provide correct quantifications of tissue displacement and strain for the beating CMs utilizing physiologically-relevant, sarcomere displacement length-based contraction criteria. The data were further synthesized into novel spatiotemporal parameters of CM contraction to account for the CM beating homogeneity, synchronicity, and propagation as holistic measures of functional myocardial tissue development. Our AR-DIC analyses may thus provide advanced non-invasive characterization tools for assessing the development of spontaneously contracting CMs, suggesting an applicability in myocardial regenerative medicine.
“…Mechanical scratch can directly damage the neurons; inflammatory cytokines in damaged neurons may release rapidly and thus affect the activity of other normal neurons. As for the mechanical stretch, it is commonly used to study the biomechanical stimulation of cardiovascular disease and bone-related diseases [ 43 , 44 ]. The neuron/axles may be damaged under equiaxial stretch (12% strain, 1.0 Hz frequency) for 4 h. In some reports, LPS usually has been used to induce inflammation and pyroptosis of macrophages [ 23 , 36 ].…”
BackgroundTraumatic brain injury (TBI) is a critical public health and socioeconomic problem throughout the world. Inflammation-induced secondary injury is one of the vital pathogenic parameters of TBI. Molecular signaling cascades of pyroptosis, a specific type of cellular necrosis, are key drivers of TBI-induced inflammation.MethodsIn this study, mice with genetically ablated caspase-1 (caspase-1−/−) were subjected to controlled cortical impact injury in vivo, and primary neuron deficient in caspase-1 through siRNA knockdown and pharmacologic inhibition was stimulated by mechanical scratch, equiaxial stretch, and LPS/ATP in vitro. We evaluated the effects of caspase-1 deficiency on neurological deficits, inflammatory factors, histopathology, cell apoptosis, and pyroptosis.ResultsDuring the acute post-injury period (0–48 h) in vivo, motor deficits, anti-inflammatory cytokines (TGF-β and IL-10), pro-inflammatory cytokines (IFN-γ, IL-1β, and IL-18), and blood lactate dehydrogenase (LDH), as well as pyroptosis-related proteins (caspase-1, caspase-1 fragments, caspase-11 and GSDMD), were increased. Caspase-1 was activated in the cortex of TBI mice. Inflammatory activation was more profound in injured wild-type mice than in caspase-1−/− mice. In vitro, mechanical scratch, equiaxial stretch, and LPS/ATP-induced neuron pyroptosis, apoptosis, LDH release, and increased expression of inflammatory factors. The effects of mechanical and inflammatory stress were reduced through inhibition of caspase-1 activity through siRNA knockdown and pharmacologic inhibition.ConclusionCollectively, these data demonstrate that pyroptosis is involved in neuroinflammation and neuronal injury after TBI, and ablation of caspase-1 inhibits TBI-induced pyroptosis. Our findings suggest that caspase-1 may be a potential target for TBI therapy.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1083-y) contains supplementary material, which is available to authorized users.
“…However, an overloaded cell tends to undergo apoptosis or necrosis. In addition to the mechanical load, the type of cell (e.g., chondrocytes, keratoconus fibroblasts, and pluripotent embryonic stem cells) may also respond disparately to DOI: 10.1159/000490239 mechanical stimulation [Sun et al, 2016;Du et al, 2017;Shradhanjali et al, 2017].…”
Mechanical stretch may cause myoblasts to either proliferate or undergo apoptosis. Identifying the molecular events that switch the fate of a stretched cell from proliferation to apoptosis is practically important in the field of regenerative medicine. A recent study on vascular smooth muscle cells illustrated that identification of these events may be achieved by addressing the stretch-induced opposite cellular outcomes simultaneously within a single investigation. To define conditions or a model in which both proliferation and apoptosis can be studied at the same time, we exposed in vitro cultured C2C12 myoblasts to a cyclic mechanical stretch regimen of 15% elongation at a stretching frequency of 1 Hz for 0, 2, 4, 6, or 8 h every day, consecutively, for 3 days. Both proliferation and apoptosis were observed. Moreover, as the duration of the stretch was prolonged, cell proliferation increased until it peaked at the optimal stretching duration. Afterwards, apoptosis gradually prevailed. Therefore, we established a model in which stretch-induced cell proliferation and apoptosis can be studied simultaneously.
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