Degradation and protrusion are key to cellular barrier breaching in cancer metastasis and leukocyte extravasation. Cancerous invadopodia and myelomonocytic podosomes are widely considered as structural tools facilitating these processes and are thus summarized under the term invadosomes. Despite similar behaviour on the individual scale, substantial differences have been reported to arise on the collective scale. They are considered to be a result of podosome mesoscale-connectivity. In this study, we investigated global in-plane and out-of-plane mechanical forces of podosome clusters in ER-Hoxb8 cell derived monocytes. We are able to correlate these forces with the interpodosomal connectivity. The observed traction and protrusion patterns fail to be explained by summation of single podosome mechanics. Instead, they appear to originate from superimposed mesoscale effects. Based on mechanistic and morphological similarities with epithelial monolayer mechanics, we propose a spatiotemporal model of podosome cluster mechanics capable of relating single to collective podosome mechanical behaviour. Our results suggest that network contraction-driven (in-plane) tractions lead to a buckling instability that contributes to the out-of-plane indentation into the substrate. First assigning an active mechanical role to the dorsal podosome actomyosin network, we aim at translating actomyosin hierarchy into scale dependency of podosome mechanics.

中文翻译：

---

单核细胞中的 2.5D 牵引揭示了基底缩进细胞突出过程中足体的中尺度力学

降解和突出是癌症转移和白细胞外渗中细胞屏障破坏的关键。癌性侵袭伪足和骨髓单核细胞足小体被广泛认为是促进这些过程的结构工具，因此在术语侵袭小体下进行了总结。尽管个人尺度上的行为相似，但据报道在集体尺度上出现了重大差异。它们被认为是足体中尺度连接的结果。在这项研究中，我们研究了 ER-Hoxb8 细胞衍生的单核细胞中足体簇的整体平面内和平面外机械力。我们能够将这些力与 interpodosomal 连接相关联。观察到的牵引和突出模式无法通过单个足体力学的总和来解释。反而，它们似乎源于叠加的中尺度效应。基于与上皮单层力学的机械和形态相似性，我们提出了一种能够将单个足体机械行为与集体足体机械行为相关联的足体簇力学时空模型。我们的结果表明，网络收缩驱动的（平面内）牵引导致屈曲不稳定性，从而导致平面外压入基板。首先为背足小体肌动球蛋白网络分配一个积极的机械作用，我们的目标是将肌动球蛋白层次转化为足体力学的尺度依赖性。我们提出了一个能够将单个与集体足体机械行为联系起来的足体集群力学时空模型。我们的结果表明，网络收缩驱动的（平面内）牵引导致屈曲不稳定性，从而导致平面外压入基板。首先为背足小体肌动球蛋白网络分配一个积极的机械作用，我们的目标是将肌动球蛋白层次转化为足体力学的尺度依赖性。我们提出了一个能够将单个与集体足体机械行为联系起来的足体集群力学时空模型。我们的结果表明，网络收缩驱动的（平面内）牵引导致屈曲不稳定性，从而导致平面外压入基板。首先为背足小体肌动球蛋白网络分配一个积极的机械作用，我们的目标是将肌动球蛋白层次转化为足体力学的尺度依赖性。