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超声诱导的应变细胞骨架重排:一项实验与模拟研究。

Ultrasound induced strain cytoskeleton rearrangement: An experimental and simulation study.

作者信息

Samandari Mohamadmahdi, Abrinia Karen, Mokhtari-Dizaji Manijhe, Tamayol Ali

机构信息

School of Mechanical Engineering, College of Engineering, University of Tehran, Tehran 11155-4563, Iran; Biomaterials Innovation Research Center, Division of Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.

School of Mechanical Engineering, College of Engineering, University of Tehran, Tehran 11155-4563, Iran.

出版信息

J Biomech. 2017 Jul 26;60:39-47. doi: 10.1016/j.jbiomech.2017.06.003. Epub 2017 Jun 20.

Abstract

Cytoskeleton and specially actin filaments are responsible for mechanical modulation of cellular behavior. These structures could be fluidized in response to transient mechanical cues. Ultrasound devices have been widely used in medicine which their generated ultrasonic waves could disrupt/fluidize actin filaments in cytoskeleton and thus could affect cellular organization. Present research aims at revealing the mechanism of fluidization caused by ultrasound induced strains. First, a numerical simulation was performed to reveal the effect of oscillating ultrasonic pressure on induced deformation in the cell with respect to different cell geometries and exposure conditions. The model revealed that higher pressure and frequencies induce higher levels of strain in the cell. The results also showed that spread cells are more exposed to cytomechanical remodeling due to higher level of ultrasound induced deformations but also the effect of harmonic excitation decreases with spreading. Furthermore, strain values found to be less in the nucleus comparing the value in the cytoplasm, but still these strains can affect the behavior of the cell through mechanotransduction mechanisms. Then, different experimental ultrasound protocols were used to evaluate their effects on cell viability and actin cytoskeleton distribution. Results of Live/Dead assay indicated that high pressure and duration of the exposure had negative effects on the viability of C2C12 cells, while the viability ratio still remained above 85%. In addition, actin fluorescent staining showed that high levels of filament disruption could occur with increasing the pressure. The results of this study shed light on cellular response to mechanical stimuli applied by ultrasonic waves.

摘要

细胞骨架,特别是肌动蛋白丝,负责对细胞行为进行机械调节。这些结构可响应瞬态机械信号而发生流化。超声设备已在医学中广泛应用,其产生的超声波可破坏/流化细胞骨架中的肌动蛋白丝,从而影响细胞组织。目前的研究旨在揭示超声诱导应变引起流化的机制。首先,进行了数值模拟,以揭示振荡超声压力对不同细胞几何形状和暴露条件下细胞诱导变形的影响。该模型表明,更高的压力和频率会在细胞中诱导更高水平的应变。结果还表明,铺展的细胞由于更高水平的超声诱导变形而更容易受到细胞力学重塑的影响,但谐波激发的影响也会随着铺展而降低。此外,发现细胞核中的应变值比细胞质中的小,但这些应变仍可通过机械转导机制影响细胞行为。然后,使用不同的实验超声方案来评估它们对细胞活力和肌动蛋白细胞骨架分布的影响。活/死检测结果表明,高压和暴露持续时间对C2C12细胞的活力有负面影响,而活力比率仍保持在85%以上。此外,肌动蛋白荧光染色表明,随着压力增加,可能会发生高水平的丝破坏。本研究结果揭示了细胞对超声波施加的机械刺激的反应。

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