Chemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes
Abstract Immune cells, such as macrophages and dendritic cells, can utilize podosomes, mechanosensitive actin-rich protrusions, to generate forces, migrate, and patrol for foreign antigens. Individual podosomes probe their microenvironment through periodic protrusion and retraction cycles (height os...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38598-z |
| _version_ | 1797817917978443776 |
|---|---|
| author | Ze Gong Koen van den Dries Rodrigo A. Migueles-Ramírez Paul W. Wiseman Alessandra Cambi Vivek B. Shenoy |
| author_facet | Ze Gong Koen van den Dries Rodrigo A. Migueles-Ramírez Paul W. Wiseman Alessandra Cambi Vivek B. Shenoy |
| author_sort | Ze Gong |
| collection | DOAJ |
| description | Abstract Immune cells, such as macrophages and dendritic cells, can utilize podosomes, mechanosensitive actin-rich protrusions, to generate forces, migrate, and patrol for foreign antigens. Individual podosomes probe their microenvironment through periodic protrusion and retraction cycles (height oscillations), while oscillations of multiple podosomes in a cluster are coordinated in a wave-like fashion. However, the mechanisms governing both the individual oscillations and the collective wave-like dynamics remain unclear. Here, by integrating actin polymerization, myosin contractility, actin diffusion, and mechanosensitive signaling, we develop a chemo-mechanical model for podosome dynamics in clusters. Our model reveals that podosomes show oscillatory growth when actin polymerization-driven protrusion and signaling-associated myosin contraction occur at similar rates, while the diffusion of actin monomers drives wave-like coordination of podosome oscillations. Our theoretical predictions are validated by different pharmacological treatments and the impact of microenvironment stiffness on chemo-mechanical waves. Our proposed framework can shed light on the role of podosomes in immune cell mechanosensing within the context of wound healing and cancer immunotherapy. |
| first_indexed | 2024-03-13T09:00:33Z |
| format | Article |
| id | doaj.art-775b22489b014ba3bc8e20dd4e6e25ab |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T09:00:33Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-775b22489b014ba3bc8e20dd4e6e25ab2023-05-28T11:20:45ZengNature PortfolioNature Communications2041-17232023-05-0114111310.1038/s41467-023-38598-zChemo-mechanical diffusion waves explain collective dynamics of immune cell podosomesZe Gong0Koen van den Dries1Rodrigo A. Migueles-Ramírez2Paul W. Wiseman3Alessandra Cambi4Vivek B. Shenoy5Center for Engineering Mechanobiology, University of PennsylvaniaDepartment of Medical Biosciences, Radboud University Medical CenterDepartments of Chemistry and Physics, McGill UniversityDepartments of Chemistry and Physics, McGill UniversityDepartment of Medical Biosciences, Radboud University Medical CenterCenter for Engineering Mechanobiology, University of PennsylvaniaAbstract Immune cells, such as macrophages and dendritic cells, can utilize podosomes, mechanosensitive actin-rich protrusions, to generate forces, migrate, and patrol for foreign antigens. Individual podosomes probe their microenvironment through periodic protrusion and retraction cycles (height oscillations), while oscillations of multiple podosomes in a cluster are coordinated in a wave-like fashion. However, the mechanisms governing both the individual oscillations and the collective wave-like dynamics remain unclear. Here, by integrating actin polymerization, myosin contractility, actin diffusion, and mechanosensitive signaling, we develop a chemo-mechanical model for podosome dynamics in clusters. Our model reveals that podosomes show oscillatory growth when actin polymerization-driven protrusion and signaling-associated myosin contraction occur at similar rates, while the diffusion of actin monomers drives wave-like coordination of podosome oscillations. Our theoretical predictions are validated by different pharmacological treatments and the impact of microenvironment stiffness on chemo-mechanical waves. Our proposed framework can shed light on the role of podosomes in immune cell mechanosensing within the context of wound healing and cancer immunotherapy.https://doi.org/10.1038/s41467-023-38598-z |
| spellingShingle | Ze Gong Koen van den Dries Rodrigo A. Migueles-Ramírez Paul W. Wiseman Alessandra Cambi Vivek B. Shenoy Chemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes Nature Communications |
| title | Chemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes |
| title_full | Chemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes |
| title_fullStr | Chemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes |
| title_full_unstemmed | Chemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes |
| title_short | Chemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes |
| title_sort | chemo mechanical diffusion waves explain collective dynamics of immune cell podosomes |
| url | https://doi.org/10.1038/s41467-023-38598-z |
| work_keys_str_mv | AT zegong chemomechanicaldiffusionwavesexplaincollectivedynamicsofimmunecellpodosomes AT koenvandendries chemomechanicaldiffusionwavesexplaincollectivedynamicsofimmunecellpodosomes AT rodrigoamiguelesramirez chemomechanicaldiffusionwavesexplaincollectivedynamicsofimmunecellpodosomes AT paulwwiseman chemomechanicaldiffusionwavesexplaincollectivedynamicsofimmunecellpodosomes AT alessandracambi chemomechanicaldiffusionwavesexplaincollectivedynamicsofimmunecellpodosomes AT vivekbshenoy chemomechanicaldiffusionwavesexplaincollectivedynamicsofimmunecellpodosomes |