Dynamic Viscoelasticity of Actin Cross-Linked with Wild-Type and Disease-Causing Mutant α-Actinin-4

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Original entry: Warren Lloyd Ung, APPHY 225, Fall 2009

"Dynamic Viscoelasticity of Actin Cross-Linked with Wild-Type and Disease-Causing Mutant α-Actinin-4"
S. M. Volkner Ward, A. Weins, M. R. Pollak, & D.A. Weitz, (2008).
Biophysical Journal.

UNDER CONSTRUCTION

Soft Matter Keywords

biopolymer network, viscoelasticity, actin

Summary

The authors used rheological methods to elucidate the effects of mutant α-actinin-4 on networks of actin biopolymers. Actin is a biopolymer commonly found in cells as double-stranded filaments. Actin filaments are part of the cellular cytoskeleton and allow the cell to exert mechanical force, maintain cellular shape, and promote intracellular transport [1]. Actin forms an integral part of muscles cells.

Gels formed with pure actin behave like a viscoelastic solid with a small elastic modulus (0.1 to 1Pa). Adding cross-links strengthens the gel or can cause actin to aggregate into larger bundles, which influence the bulk viscoelastic properties. Of particular interest is a cross-linker called α-actinin-4. This cross-linker is present naturally in podocytes, the kidney cells responsible for the filtration of wastes. Mutations in the cross-linking protein results in problems for the cells expressing the mutation. Actin aggregates preventing normal function. A single point mutation in this protein may be significant enough to cause kidney failure in extreme cases. Figure 1 below shows actin networks with and without α-actinin-4 cross-linker.

Figure 1: Actin stained with phalloidin: (A) no cross-linker, (B) wild-type α-actinin-4, and (C) mutant α-actinin-4. Scale bar is <math>40\mum</math>

By performing rheological experiments which compare the response of both the wild-type and mutant α-actinin-4, the authors confirm results obtained to date, and propose two possible mechanisms, which explain the differences between mutant and wild-type α-actinin-4.

Figure 2: Frequency dependence of elastic modulus (solid) and viscous modulus (outline) for wild-type (circles) and mutant (triangles) α-actinin-4.
Figure 3:

Soft Matter Discussion

The rheological properties, which are examined in these experiments, are the elastic modulus (G') and the viscous modulus (G) with respect to frequency (see Figure 2). For both mutant and wild-type cross-linker, there is a plateau in the elastic modulus; the plateau is more pronounced in networks with the mutant cross-linker. This plateau occurs at <math>f_{plateau}</math>, which corresponds to the minimum in the viscous modulus. For mutant cross-linker, this plateau frequences tends towards lower values. As a viscoelastic material, we expect the elastic modulus and viscous modulus to converge for long timescales, while the viscous modulus dominates for long timescales.

Increasing the concentration of cross-linker pushes

Applications

By determining the mechanism, which causes mutant α-actinin-4 to behave distinctly from wild-type cross-linker, it is possible to begin treating the serious kidney diseases, which may result.

References

  1. "Cytoskeleton." Wikipedia.