Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell Migration
Cell migration in confining physiological environments relies on the concerted dynamics of several cellular components, including protrusions, adhesions with the environment, and the cell nucleus. However, it remains poorly understood how the dynamic interplay of these components and the cell polari...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Physical Society
2022-09-01
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| Series: | Physical Review X |
| Online Access: | http://doi.org/10.1103/PhysRevX.12.031041 |
| _version_ | 1811272065043398656 |
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| author | David B. Brückner Matthew Schmitt Alexandra Fink Georg Ladurner Johannes Flommersfeld Nicolas Arlt Edouard Hannezo Joachim O. Rädler Chase P. Broedersz |
| author_facet | David B. Brückner Matthew Schmitt Alexandra Fink Georg Ladurner Johannes Flommersfeld Nicolas Arlt Edouard Hannezo Joachim O. Rädler Chase P. Broedersz |
| author_sort | David B. Brückner |
| collection | DOAJ |
| description | Cell migration in confining physiological environments relies on the concerted dynamics of several cellular components, including protrusions, adhesions with the environment, and the cell nucleus. However, it remains poorly understood how the dynamic interplay of these components and the cell polarity determine the emergent migration behavior at the cellular scale. Here, we combine data-driven inference with a mechanistic bottom-up approach to develop a model for protrusion and polarity dynamics in confined cell migration, revealing how the cellular dynamics adapt to confining geometries. Specifically, we use experimental data of joint protrusion-nucleus migration trajectories of cells on confining micropatterns to systematically determine a mechanistic model linking the stochastic dynamics of cell polarity, protrusions, and nucleus. This model indicates that the cellular dynamics adapt to confining constrictions through a switch in the polarity dynamics from a negative to a positive self-reinforcing feedback loop. Our model further reveals how this feedback loop leads to stereotypical cycles of protrusion-nucleus dynamics that drive the migration of the cell through constrictions. These cycles are disrupted upon perturbation of cytoskeletal components, indicating that the positive feedback is controlled by cellular migration mechanisms. Our data-driven theoretical approach therefore identifies polarity feedback adaptation as a key mechanism in confined cell migration. |
| first_indexed | 2024-04-12T22:33:38Z |
| format | Article |
| id | doaj.art-2714971b895b41e6adb8e48060650ded |
| institution | Directory Open Access Journal |
| issn | 2160-3308 |
| language | English |
| last_indexed | 2024-04-12T22:33:38Z |
| publishDate | 2022-09-01 |
| publisher | American Physical Society |
| record_format | Article |
| series | Physical Review X |
| spelling | doaj.art-2714971b895b41e6adb8e48060650ded2022-12-22T03:13:55ZengAmerican Physical SocietyPhysical Review X2160-33082022-09-0112303104110.1103/PhysRevX.12.031041Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell MigrationDavid B. BrücknerMatthew SchmittAlexandra FinkGeorg LadurnerJohannes FlommersfeldNicolas ArltEdouard HannezoJoachim O. RädlerChase P. BroederszCell migration in confining physiological environments relies on the concerted dynamics of several cellular components, including protrusions, adhesions with the environment, and the cell nucleus. However, it remains poorly understood how the dynamic interplay of these components and the cell polarity determine the emergent migration behavior at the cellular scale. Here, we combine data-driven inference with a mechanistic bottom-up approach to develop a model for protrusion and polarity dynamics in confined cell migration, revealing how the cellular dynamics adapt to confining geometries. Specifically, we use experimental data of joint protrusion-nucleus migration trajectories of cells on confining micropatterns to systematically determine a mechanistic model linking the stochastic dynamics of cell polarity, protrusions, and nucleus. This model indicates that the cellular dynamics adapt to confining constrictions through a switch in the polarity dynamics from a negative to a positive self-reinforcing feedback loop. Our model further reveals how this feedback loop leads to stereotypical cycles of protrusion-nucleus dynamics that drive the migration of the cell through constrictions. These cycles are disrupted upon perturbation of cytoskeletal components, indicating that the positive feedback is controlled by cellular migration mechanisms. Our data-driven theoretical approach therefore identifies polarity feedback adaptation as a key mechanism in confined cell migration.http://doi.org/10.1103/PhysRevX.12.031041 |
| spellingShingle | David B. Brückner Matthew Schmitt Alexandra Fink Georg Ladurner Johannes Flommersfeld Nicolas Arlt Edouard Hannezo Joachim O. Rädler Chase P. Broedersz Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell Migration Physical Review X |
| title | Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell Migration |
| title_full | Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell Migration |
| title_fullStr | Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell Migration |
| title_full_unstemmed | Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell Migration |
| title_short | Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell Migration |
| title_sort | geometry adaptation of protrusion and polarity dynamics in confined cell migration |
| url | http://doi.org/10.1103/PhysRevX.12.031041 |
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