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.
Ward
Sabine M Volkmer
SM
Department of Physics and School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA.
Weins
Astrid
A
Pollak
Martin R
MR
Weitz
David A
DA
D000185:Actinin / Q000737:chemistry* / Q000648:ultrastructure; D000199:Actins / Q000737:chemistry* / Q000648:ultrastructure; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D004548:Elasticity; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism; D051379:Mice; D008956:Models, Chemical; D009154:Mutation; D011485:Protein Binding; D014783:Viscosity
D000199:Actins; C491752:Actn4 protein, mouse; D000185:Actinin