A new approach to model cross-linked actin networks: multi-scale continuum formulation and computational analysis
Michael J Unterberger1, Kurt M Schmoller, Andreas R Bausch
1Institute of Biomechanics, Center of Biomedical Engineering, Graz University of Technology, Kronesgasse 5-I, 8010 Graz, Austria.
Journal of the Mechanical Behavior of Biomedical Materials
|April 23, 2013
Summary
This study presents a continuum mechanical model for the actin cortex, a key component of cellular mechanical properties. The model accurately describes the nonlinear behavior of filamentous actin networks, validated by experimental data.
Area of Science:
- Biophysics
- Cell Mechanics
- Materials Science
Background:
- Cellular mechanical properties are primarily determined by the cytoskeleton.
- The actin cortex, a densely cross-linked protein network beneath the lipid bilayer, significantly contributes to cellular mechanics.
- Understanding the actin cortex's mechanical behavior is crucial for cell biology and biophysics.
Purpose of the Study:
- To develop a continuum mechanical formulation for modeling the mechanical properties of in vitro actin networks.
- To describe the behavior of individual actin filaments and their spatial arrangement within the network.
- To validate the model against experimental data from reconstituted actin networks.
Main Methods:
- A continuum mechanical formulation was developed, neglecting viscous effects and considering the network as elastic.
- The nonlinear force-stretch relationship of filamentous actin was modeled using an extensible worm-like chain model (β-model).
- A non-affine micro-sphere network was employed to extend 2D properties to 3D, accounting for spatially distributed filaments. The model was implemented in a finite element program.
Main Results:
- The β-model accurately describes the nonlinear force-stretch relationship of individual actin filaments.
- The continuum mechanical model, incorporating micro-structural properties, accurately predicts the strain-energy density of reconstituted actin networks.
- The model yields Cauchy stress and elasticity tensors, validated through rheological experiments.
Conclusions:
- The developed continuum mechanical model effectively captures the elastic properties of actin networks based on their micro-structure.
- The model provides a framework for understanding and predicting the mechanical behavior of the actin cortex.
- This work offers a valuable tool for simulating cellular mechanical responses in various biological contexts.
Related Concept Videos
Formation of Higher-order Actin Filaments
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...
Generation of Straight or Branched Actin Filaments
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
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.
Actin Polymerization and Cell Motility
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.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate.
Actin Polymerization
Actin polymerization occurs through the head-to-tail association of binding sites on monomeric actin or G-actin to form filamentous or F-actin. The polymerization can be divided into three phases ̶ nucleation, elongation, and steady-state phase.
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight actin...
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight actin...
Actin Filament Depolymerization
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
In F-actin, the ADF/cofilin proteins...

