Cell migration and invasion is a key driving factor for providing essential cellular functions under physiological conditions or the malignant progression of tumors following downward the metastatic cascade. Although there has been plentiful of molecules identified to support the migration and invasion of cells, the mechanical aspects have not yet been explored in a combined and systematic manner. In addition, the cellular environment has been classically and frequently assumed to be homogeneous for reasons of simplicity. However, motility assays have led to various models for migration covering only some aspects and supporting factors that in some cases also include mechanical factors. Instead of specific models, in this review, a more or less holistic model for cell motility in 3D is envisioned covering all these different aspects with a special emphasis on the mechanical cues from a biophysical perspective. After introducing the mechanical aspects of cell migration and invasion and presenting the heterogeneity of extracellular matrices, the three distinct directions of cell motility focusing on the mechanical aspects are presented. These three different directions are as follows: firstly, the commonly used invasion tests using structural and structure-based mechanical environmental signals; secondly, the mechano-invasion assay, in which cells are studied by mechanical forces to migrate and invade; and thirdly, cell mechanics, including cytoskeletal and nuclear mechanics, to influence cell migration and invasion. Since the interaction between the cell and the microenvironment is bi-directional in these assays, these should be accounted in migration and invasion approaches focusing on the mechanical aspects. Beyond this, there is also the interaction between the cytoskeleton of the cell and its other compartments, such as the cell nucleus. In specific, a three-element approach is presented for addressing the effect of mechanics on cell migration and invasion by including the effect of the mechano-phenotype of the cytoskeleton, nucleus and the cell’s microenvironment into the analysis. In precise terms, the combination of these three research approaches including experimental techniques seems to be promising for revealing bi-directional impacts of mechanical alterations of the cellular microenvironment on cells and internal mechanical fluctuations or changes of cells on the surroundings. Finally, different approaches are discussed and thereby a model for the broad impact of mechanics on cell migration and invasion is evolved.

细胞迁移和侵袭是在生理条件下提供基本细胞功能或肿瘤沿转移级联向下恶性进展的关键驱动因素。尽管已经鉴定出大量支持细胞迁移和侵袭的分子，但尚未以组合和系统的方式对其机械方面进行探索。此外，出于简单性的原因，细胞环境通常被假设为同质的。然而，运动测定导致了各种迁移模型，仅涵盖某些方面和支持因素，在某些情况下还包括机械因素。在这篇综述中，我们设想了一个或多或少整体的 3D 细胞运动模型，而不是特定的模型，涵盖所有这些不同的方面，并特别强调从生物物理角度来看的机械线索。在介绍了细胞迁移和侵袭的力学方面以及细胞外基质的异质性之后，提出了以力学方面为重点的细胞运动的三个不同方向。这三个不同的方向如下：第一，常用的利用结构和基于结构的机械环境信号的入侵测试；其次，机械侵袭实验，通过机械力研究细胞的迁移和侵袭；第三，细胞力学，包括细胞骨架和核力学，影响细胞迁移和侵袭。由于在这些测定中细胞和微环境之间的相互作用是双向的，因此在侧重于机械方面的迁移和侵袭方法中应考虑这些相互作用。 除此之外，细胞的细胞骨架与其其他区室（例如细胞核）之间也存在相互作用。具体来说，提出了一种三要素方法，通过将细胞骨架、细胞核和细胞微环境的力学表型的影响纳入分析，来解决力学对细胞迁移和侵袭的影响。准确地说，包括实验技术在内的这三种研究方法的结合似乎有望揭示细胞微环境的机械变化对细胞的双向影响以及细胞内部的机械波动或细胞对周围环境的变化。最后，讨论了不同的方法，从而形成了力学对细胞迁移和侵袭的广泛影响的模型。