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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.