Two competing orientation patterns explain experimentally observed anomalies in growing actin networks
Julian Weichsel1, Ulrich S Schwarz
1Bioquant, and Institute for Theoretical Physics, Heidelberg University, 69120 Heidelberg, Germany.
Summary
A new model explains actin network dynamics during cell migration. It shows how filament branching and capping influence force-velocity relations, resolving conflicting experimental data and revealing hysteresis.
Area of Science:
- Cell biology
- Biophysics
- Actin dynamics
Background:
- Cell migration relies on lamellipodium protrusion driven by branched actin networks.
- In vitro studies show conflicting force-velocity relations for these networks, including convex/concave shapes and history dependence.
Purpose of the Study:
- To develop a generic model explaining the anomalous force-velocity relations observed in actin networks.
- To investigate how actin filament branching and capping influence network stability and dynamics.
Main Methods:
- Modeling actin network branching as a reaction independent of filament number.
- Modeling capping as proportional to the existing filament number.
- Utilizing stochastic network simulations and deterministic rate equations.
Main Results:
- The model predicts two stable network states: +/- 35 degrees and +70/0/-70 degrees orientation patterns.
- Changes in network growth velocity trigger transitions between these states.
- The model reproduces hysteresis in actin network growth velocity under force, explaining convex and concave force-velocity relations.
Conclusions:
- A simple, generic model can reconcile conflicting experimental findings on actin network force-velocity relations.
- The model's predictions have significant implications for understanding the mechanics of cell migration.
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Arp2/3 Complex
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The polymerization of G-actin monomers into filamentous F-actin is a multi-step process. Once the F-actins are formed, they can bundle together in different arrangements to form higher-order networks and regulate cellular functions. Common examples include the formation of lamellipodia and filopodia at the cell's leading edge by actin reorganization in a migrating cell. The microvilli on the brush border epithelial cells are also formed through the F-actin network.
The high-order actin networks...
The high-order actin networks...
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Actin is a family of globular proteins that are highly abundant in eukaryotic cells. It makes up approximately 1-5% of total cell protein concentration. Actin monomers polymerize to form a complex network of polarized filaments, the actin cytoskeleton, that plays a crucial role in many cellular processes, including cell motility, division, endocytosis, and metastasis of cancer cells.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate.
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Polarity of the Cytoskeleton
The intrinsic polarity of cells can be primarily attributed to two factors- i) the asymmetric accumulation of mobile components such are regulatory molecules and subcellular components across the cell and ii) the orientation of polar cytoskeletal filaments that make up the cytoskeletal networks, specifically microfilaments, and microtubules arranged along the axis of polarity. Interactions between the cytoskeletal filaments are crucial for the establishment and maintenance of the polar nature...
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Introduction to Actin
Actin is a highly conserved cytoskeletal protein found abundantly in eukaryotic cells. It constitutes 10% weight of the total cellular protein in muscle cells, while in non-muscle cells, it is lower and makes up around 1–5 percent of the total cell protein. Actin found in the unicellular amoebae and complex multicellular animals is around 80% similar, demonstrating their conservation over a billion years of evolution. Actin coding genes are conserved within species and across different species.


