Dynamic viscoelasticity of actin cross-linked with wild-type and disease-causing mutant alpha-actinin-4.


The actin cross-linker alpha-actinin-4 has been found to be indispensable for the structural and functional integrity of podocytes; deficiency or alteration of this protein due to mutations results in kidney disease. To gain insight into the effect of the cross-linker on cytoskeletal mechanics, we studied the macroscopic rheological properties of actin networks cross-linked with wild-type and mutant alpha-actinin-4. The frequency-dependent viscoelasticity of the networks is characterized by an elastic plateau at intermediate frequencies, and relaxation toward fluid properties at low frequencies. The relaxation frequencies of networks with mutant alpha-actinin-4 are an order of magnitude lower than that with the wild-type, suggesting a slower reaction rate for the dissociation of actin and alpha-actinin for the mutant, consistent with a smaller observed equilibrium dissociation constant. This difference can be attributed to an additional binding site that is exposed as a result of the mutation, and can be interpreted as a difference in binding energy barriers. This is further supported by the Arrhenius-like temperature dependence of the relaxation frequencies.

DOI: 10.1529/biophysj.108.131722

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@article{Ward2008DynamicVO, title={Dynamic viscoelasticity of actin cross-linked with wild-type and disease-causing mutant alpha-actinin-4.}, author={Sabine M Volkmer Ward and Astrid Weins and Martin R . Pollak and David A. Weitz}, journal={Biophysical journal}, year={2008}, volume={95 10}, pages={4915-23} }