A computational modeling of invadopodia protrusion into an extracellular matrix fiber network
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s41598-022-05224-9.pdf
Description
Published version
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13.75 MB
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Checksum (MD5)
02ebce957e3930d0d837fae2b9d14d72
Author(s)
Kim, Min-Cheol
Li, Ran
Abeyaratne, Rohan
Kamm, Roger D
Asada, H Harry
Date Issued
2022
Journal
Scientific Reports
Publisher
Springer Science and Business Media LLC
Citation
Kim, Min-Cheol, Li, Ran, Abeyaratne, Rohan, Kamm, Roger D and Asada, H Harry. 2022. "A computational modeling of invadopodia protrusion into an extracellular matrix fiber network." Scientific Reports, 12 (1).
Version
Final published version
Abstract
AbstractInvadopodia are dynamic actin-rich membrane protrusions that have been implicated in cancer cell invasion and metastasis. In addition, invasiveness of cancer cells is strongly correlated with invadopodia formation, which are observed during extravasation and colonization of metastatic cancer cells at secondary sites. However, quantitative understanding of the interaction of invadopodia with extracellular matrix (ECM) is lacking, and how invadopodia protrusion speed is associated with the frequency of protrusion-retraction cycles remains unknown. Here, we present a computational framework for the characterization of invadopodia protrusions which allows two way interactions between intracellular branched actin network and ECM fibers network. We have applied this approach to predicting the invasiveness of cancer cells by computationally knocking out actin-crosslinking molecules, such as α-actinin, filamin and fascin. The resulting simulations reveal distinct invadopodia dynamics with cycles of protrusion and retraction. Specifically, we found that (1) increasing accumulation of MT1-MMP at tips of invadopodia as the duration of protrusive phase is increased, and (2) the movement of nucleus toward the leading edge of the cell becomes unstable as duration of the retractile phase (or myosin turnover time) is longer than 1 min.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
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DOI of Published Version
https://doi.org/10.1038/S41598-022-05224-9
