A computational modeling of invadopodia protrusion into an extracellular matrix fiber network
<jats:title>Abstract</jats:title><jats:p>Invadopodia 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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2023
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| Online Access: | https://hdl.handle.net/1721.1/150662 |
| _version_ | 1826202172226797568 |
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| author | Kim, Min-Cheol Li, Ran Abeyaratne, Rohan Kamm, Roger D Asada, H Harry |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Kim, Min-Cheol Li, Ran Abeyaratne, Rohan Kamm, Roger D Asada, H Harry |
| author_sort | Kim, Min-Cheol |
| collection | MIT |
| description | <jats:title>Abstract</jats:title><jats:p>Invadopodia 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.</jats:p> |
| first_indexed | 2024-09-23T12:03:20Z |
| format | Article |
| id | mit-1721.1/150662 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:03:20Z |
| publishDate | 2023 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1506622023-05-12T03:29:07Z A computational modeling of invadopodia protrusion into an extracellular matrix fiber network Kim, Min-Cheol Li, Ran Abeyaratne, Rohan Kamm, Roger D Asada, H Harry Massachusetts Institute of Technology. Department of Mechanical Engineering <jats:title>Abstract</jats:title><jats:p>Invadopodia 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.</jats:p> 2023-05-11T17:20:58Z 2023-05-11T17:20:58Z 2022 2023-05-11T17:16:45Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/150662 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). en 10.1038/S41598-022-05224-9 Scientific Reports Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Scientific Reports |
| spellingShingle | Kim, Min-Cheol Li, Ran Abeyaratne, Rohan Kamm, Roger D Asada, H Harry A computational modeling of invadopodia protrusion into an extracellular matrix fiber network |
| title | A computational modeling of invadopodia protrusion into an extracellular matrix fiber network |
| title_full | A computational modeling of invadopodia protrusion into an extracellular matrix fiber network |
| title_fullStr | A computational modeling of invadopodia protrusion into an extracellular matrix fiber network |
| title_full_unstemmed | A computational modeling of invadopodia protrusion into an extracellular matrix fiber network |
| title_short | A computational modeling of invadopodia protrusion into an extracellular matrix fiber network |
| title_sort | computational modeling of invadopodia protrusion into an extracellular matrix fiber network |
| url | https://hdl.handle.net/1721.1/150662 |
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