Department of Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Department of Physiology and Biophysics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
FASEB J. 2019 Oct;33(10):10618-10632. doi: 10.1096/fj.201900131R. Epub 2019 Jun 24.
Biomechanical cues within tissue microenvironments are critical for maintaining homeostasis, and their disruption can contribute to malignant transformation and metastasis. Once transformed, metastatic cancer cells can migrate persistently by adapting (plasticity) to changes in the local fibrous extracellular matrix, and current strategies to recapitulate persistent migration rely exclusively on the use of aligned geometries. Here, the controlled interfiber spacing in suspended crosshatch networks of nanofibers induces cells to exhibit plasticity in migratory behavior (persistent and random) and the associated cytoskeletal arrangement. At dense spacing (3 and 6 µm), unexpectedly, elongated cells migrate persistently (in 1 dimension) at high speeds in 3-dimensional shapes with thick nuclei, and short focal adhesion cluster (FAC) lengths. With increased spacing (18 and 36 µm), cells attain 2-dimensional morphologies, have flattened nuclei and longer FACs, and migrate randomly by rapidly detaching their trailing edges that strain the nuclei by ∼35%. At 54-µm spacing, kite-shaped cells become near stationary. Poorly developed filamentous actin stress fibers are found only in cells on 3-µm networks. Gene-expression profiling shows a decrease in transcriptional potential and a differential up-regulation of metabolic pathways. The consistency in observed phenotypes across cell lines supports using this platform to dissect hallmarks of plasticity in migration .-Jana, A., Nookaew, I., Singh, J., Behkam, B., Franco, A. T., Nain, A. S. Crosshatch nanofiber networks of tunable interfiber spacing induce plasticity in cell migration and cytoskeletal response.
组织微环境中的生物力学线索对于维持内稳态至关重要，其破坏可能导致恶性转化和转移。一旦发生转化，转移性癌细胞可以通过适应（可塑性）局部纤维细胞外基质的变化而持续迁移，目前重现持续迁移的策略完全依赖于使用对齐的几何形状。在这里，悬浮十字形纳米纤维网络中的受控纤维间间距诱导细胞表现出迁移行为（持续和随机）和相关细胞骨架排列的可塑性。在密集的间隔（3 和 6 µm）下，出乎意料的是，细长的细胞以高速（在 1 维中）在具有厚核和短焦点粘连簇（FAC）长度的 3 维形状中持续迁移（持久性）。随着间距的增加（18 和 36 µm），细胞获得 2 维形态，核扁平化且 FAC 更长，并通过快速脱离其尾部而随机迁移，核被拉伸约 35%。在 54 µm 的间隔下，风筝形细胞几乎处于静止状态。仅在 3 µm 网络上的细胞中发现发育不良的丝状肌动蛋白应力纤维。基因表达谱显示转录潜力下降和代谢途径的差异上调。在细胞系中观察到的表型的一致性支持使用该平台来剖析迁移可塑性的特征。-Jana，A.，Nookaew，I.，Singh，J.，Behkam，B.，Franco，A. T.，Nain，A. S. 可调纤维间间距的十字形纳米纤维网络诱导细胞迁移和细胞骨架反应的可塑性。
