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

Citation:

Ward, S. V. M. ; Weins, A. ; Pollak, M. R. ; Weitz, D. A. Dynamic viscoelasticity of actin cross-linked with wild-type and disease-causing mutant alpha-actinin-4. Biophysical Journal 2008, 95, 4915-4923. Copy at http://www.tinyurl.com/l47edh3

Abstract:

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.

Notes:

Times Cited: 13

Last updated on 04/07/2014