The regulatory role of cell mechanics for migration of differentiating myeloid cells
The regulatory role of cell mechanics for migration of differentiating myeloid cells
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DOI：
10.1073/pnas.0811261106
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发表时间：
2009-09-15
影响因子：
11.1
通讯作者：
Guck, Jochen
中科院分区：
文献类型：
--
作者：
Lautenschlaeger, Franziska;Paschke, Stephan;Guck, Jochen
细胞迁移对于组织维持、免疫反应很重要，并且在疾病中经常发生改变。虽然包括细胞粘附在内的生化方面已被详细研究，但对细胞机械性能的作用知之甚少。以前的测量方法依赖于与人造表面的接触，这可能会使结果变得复杂。在这里，我们使用非接触式微流体光学担架来研究与其他参数分离的细胞力学，在急性早幼粒细胞白血病（APL）细胞的组织浸润的背景下，这种情况发生在视黄酸分化治疗期间。 APL 细胞的顺应性测量显示分化过程中显着软化，分化细胞的机械特性与正常中性粒细胞相似。为了干扰软化后获得的迁移能力，将分化的 APL 细胞暴露于紫杉醇，紫杉醇可以稳定微管。这种治疗不会改变顺应性，但会在机械应力停止后将细胞松弛程度降低六倍，这与运动性的显着降低一致。我们的观察表明，组织浸润所需的细胞形状的动态重塑可能会因微管系统的硬化而受阻。细胞骨架、细胞力学和运动性之间的联系表明了依赖于细胞迁移的病理学的治疗选择，特别是癌症转移。
Migration of cells is important for tissue maintenance, immune response, and often altered in disease. While biochemical aspects, including cell adhesion, have been studied in detail, much less is known about the role of the mechanical properties of cells. Previous measurement methods rely on contact with artificial surfaces, which can convolute the results. Here, we used a non-contact, microfluidic optical stretcher to study cell mechanics, isolated from other parameters, in the context of tissue infiltration by acute promyelocytic leukemia (APL) cells, which occurs during differentiation therapy with retinoic acid. Compliance measurements of APL cells reveal a significant softening during differentiation, with the mechanical properties of differentiated cells resembling those of normal neutrophils. To interfere with the migratory ability acquired with the softening, differentiated APL cells were exposed to paclitaxel, which stabilizes microtubules. This treatment does not alter compliance but reduces cell relaxation after cessation of mechanical stress six-fold, congruent with a significant reduction of motility. Our observations imply that the dynamical remodeling of cell shape required for tissue infiltration can be frustrated by stiffening the microtubular system. This link between the cytokeleton, cell mechanics, and motility suggests treatment options for pathologies relying on migration of cells, notably cancer metastasis.