Understanding actin organization in cell structure through lattice based Monte Carlo simulations
Kathleen Puskar1, Leonard Apeltsin, Shlomo Ta'asan
1Department of Mechanical Engineering Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213, USA.
Mechanics & Chemistry of Biosystems : MCB
|June 21, 2006
Summary
We developed a computational method to study actin filament self-assembly, revealing distinct behaviors at realistic cell concentrations compared to simpler models. This technique simulates molecular gradients for better understanding cell mechanics.
Area of Science:
- Cellular mechanics
- Biophysics
- Computational biology
Background:
- Cell structure, shape, and motility depend on molecular components like the cytoskeleton.
- The cytoskeleton plays a crucial role in intracellular organization and mechanotransduction.
- Understanding actin filament self-assembly is key to cell mechanics.
Purpose of the Study:
- To develop a computational technique for probing actin filament self-assembly.
- To model actin polymerization using a probabilistic approach.
- To investigate the behavior of actin filaments at realistic cellular concentrations.
Main Methods:
- A lattice-based Monte Carlo method was employed.
- Actin polymerization was modeled using interactions of globular actin.
- A probabilistic model included both inert and active proteins.
- Localized mobility parameters were introduced to simulate molecular gradients.
Main Results:
- The computational model showed similar results to ordinary differential equations at low concentrations.
- A bi-phasic divergence was observed at realistic mammalian cell concentrations.
- Simulated molecular gradients mimicked in vivo nonhomogeneous protein distributions.
Conclusions:
- The developed computational technique accurately models actin filament self-assembly.
- The study highlights differences between low and realistic cellular concentrations.
- This method has potential applications in cell biology and materials self-assembly.
Related Concept Videos
01:26Introduction 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.
01:11Formation 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...
01:14Generation 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...
01:13Actin 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.
01:42Actin 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...
01:18Assembly of Cytoskeletal Filaments
Cytoskeletal filaments are polymeric forms of smaller protein subunits. However, individual cytoskeletal filaments may easily disassemble or associate with other similar filaments to form rigid structures. Microfilaments, made of actin monomers, rely on actin-binding proteins to form bundles and create networks of individual actin filaments. Microtubules rely on microtubule-associated proteins (MAPs) to form sturdy cylindrical structures. However, the proteins involved in forming complex...