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Stress fiber growth and remodeling determines cellular morphomechanics under uniaxial cyclic stretch

机译:应力纤维生长和重塑决定了单轴循环拉伸下的细胞形态力学

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摘要

Stress fibers in the cytoskeleton are essential in maintaining cellular shape and influence cellular adhesion and migration. Cyclic uniaxial stretching results in cellular reorientation orthogonal to the applied stretch direction. The mechanistic cues underlying changes to cellular form and function to stretch stimuli are currently underexplored. We show stretch-induced stress fiber lengthening, their realignment, and increased cortical actin in NIH 3T3 fibroblasts stretched over varied amplitudes and durations. Higher amounts of actin and stress fiber alignment were accompanied with an increase in the effective elastic modulus of cells. Microtubules did not contribute to the measured stiffness or reorientation response but were essential to the nuclear reorientation. We used a phenomenological growth and remodeling law, based on the experimental data, to model stress fiber elongation and reorientation dynamics based on a nonlinear, orthotropic, fiber-reinforced continuum representation of the cell. The model predicts the changes observed fibroblast morphology and increased cellular stiffness under uniaxial cyclic stretch which agrees with experimental results. Such studies are important in exploring the differences underlying mechanotransduction and cellular contractility under stretch.
机译:细胞骨架中的应力纤维对于维持细胞形状和影响细胞粘附和迁移至关重要。循环单轴拉伸导致细胞重新定向与施加的拉伸方向正交。细胞形态和功能变化以拉伸刺激的机制线索目前尚未得到充分探索。我们显示了拉伸诱导的应力纤维延长、它们的重新排列以及 NIH 3T3 成纤维细胞中皮质肌动蛋白的增加,这些成纤维细胞在不同幅度和持续时间上拉伸。肌动蛋白和应力纤维排列量的增加伴随着细胞有效弹性模量的增加。微管对测量的刚度或重新定向反应没有贡献,但对核重新定向至关重要。我们使用基于实验数据的唯象生长和重塑定律,基于细胞的非线性、正交各向异性、纤维增强连续体表示来模拟应力纤维伸长和重新取向动力学。该模型预测了单轴循环拉伸下观察到的成纤维细胞形态变化和细胞刚度增加,与实验结果一致。这些研究对于探索拉伸下机械转导和细胞收缩力的差异非常重要。

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