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Engineered ridge and micropillar array detectors to quantify the directional migration of fibroblasts

机译:工程脊和微储物阵列探测器,以量化成纤维细胞的定向迁移

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摘要

Cell migrations on substrates are important in diverse processes such as wound healing, embryogenesis, and pathologies like cancer metastasis. An understanding of the cellular mechanobiology during migration requires development of suitable engineering platforms to better represent the anisotropic in vivo cellular environment and measure traction forces due to cell adhesion. We fabricated a custom elastomeric micropillar array detector (mPAD), comprised of alternate ridge and pillar topographical features, using a lithographic fabrication method that creates an anisotropic microenvironment and also permits the measurement of traction forces. We used the finite element method to compare predictions of calculated tractions for pillar geometries with different aspect ratios using linear and nonlinear constitutive models. These simulations showed the importance of pillar aspect ratios and constitutive models in computing resulting tractions. We cultured 3T3 fibroblasts on the engineered mPAD and characterized cellular migrations over a three hour period. Our results show highly elongated cellular and nuclear morphologies on the mPAD substrates as compared to cells cultured on control elastomeric substrates. Cells on mPADs demonstrated persistent directional motion along ridges as compared to random movements on control substrates. These results showed the importance of substrate anisotropy in the alignment of fibroblasts on mPAD. We also measured differences in the cellular tractions along the length of the cell on mPAD substrates. Engineered mPADs are hence useful in directing cellular motions and in delineating mechanobiological processes during adhesion and migration.
机译:在底物上的细胞迁移在不同的过程中是重要的,例如伤口愈合,胚胎发生和癌症转移等病理学。在迁移过程中对细胞力学学的理解需要开发合适的工程平台,以更好地代表体内细胞环境中的各向异性,并且由于细胞粘附而测量牵引力。我们制造了一种定制的弹性微米阵列检测器(MPAD),其包括替代脊和柱状特征,所述光刻制造方法包括产生各向异性微环境并且还允许测量牵引力。我们使用了有限元方法来比较使用线性和非线性本构模型的不同纵横比计算柱几何形状的预测。这些模拟表明,在计算所产生的诉讼中,柱纵横比和本构模型的重要性。我们在工程的MPAD上培养了3T3成纤维细胞,并在三个小时内表征了细胞迁移。与在对照弹性体基材上培养的细胞相比,我们的结果显示了MPAD底物上的高度细长细胞和核形态。与对照基板上的随机运动相比,MPAD上的细胞显示沿脊的持续定向运动。这些结果表明,底物各向异性在成纤维细胞对MPAD上的对准中的重要性。我们还沿着MPAD衬底的细胞的长度测量了细胞诉粒度的差异。因此,工程的MPADS在粘附和迁移期间有用用于引导细胞运动和描绘机械过程。

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  • 来源
    《RSC Advances》 |2017年第81期|共8页
  • 作者单位

    Seoul Natl Univ Sch Mech &

    Aerosp Engn Seoul 151744 South Korea;

    Indian Inst Sci Dept Mech Engn Bangalore 560012 Karnataka India;

    Indian Inst Sci Dept Mech Engn Bangalore 560012 Karnataka India;

    Indian Inst Sci Dept Mech Engn Bangalore 560012 Karnataka India;

    Chonnam Natl Univ Gwangju South Korea;

    Indian Inst Sci Dept Mech Engn Bangalore 560012 Karnataka India;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
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