The Mechanical Properties of a Utrophin Construct Encoding the Tandem CH Actin Binding Domain through Spectrin Repeat 3 is Altered by the Cell Expression System through Post-Translational Modifications

Abstract

Duchenne muscular dystrophy (DMD) is a lethal muscle wasting disease caused by the absence of dystrophin protein. Utrophin is a dystrophin homologue currently under investigation as a replacement therapy for DMD. Dystrophin and utrophin are hypothesized to function as molecular shock absorbers to mechanically stabilize the muscle cell membrane. Recently, we published atomic force microscopy data showing that utrophin is much stiffer than data previously reported for dystrophin. Here we show that the cell expression system employed impacts both the post-translational modification and mechanical behavior of a utrophin construct encoding the N-terminal actin binding domain through spectrin repeat 3 (UtrN-R3).