Multisuction Electrode Arrays to Investigate Multi-Sensory Integration in Neural Tissue

3354-Pos Board B459 Recombinant MG53 Binds Lipid Signals on Damaged Cell Membranes to Increase Membrane Repair Capacity Noah Weisleder, Norio Takizawa, PeiHui Lin, Tao Tan, Pinjung Chen, Rosalie Yan, Xiaoli Zhao, Moonsun Hwang, Hiroshi Takeshima, Jianjie Ma. Plasma membrane repair is a highly conserved mechanism that appears in most eukaryotic cells. While a simple lipid bilayer will reseal through thermodynamic principles, the presence of a cytoskeleton results in the native plasma membrane being held under tension, thus some disruptions the plasma membrane cannot spontaneously reseal. Previous studies established that plasma membrane repair is an active process involving translocation of intracellular vesicles to the injury site and fusion of these vesicles to form a repair ‘‘patch’’. An emerging concept in cell biology establishes this intrinsic membrane repair/ regeneration process is a fundamental aspect of normal physiology and that disruption of this mechanism underlies the progression of many human diseases, including cardiovascular disease, neurodegeneration, ischemic injury and muscular dystrophy. We recently discovered that mitsugumin 53 (MG53/TRIM72) is an essential component of the cell membrane repair. In this study we tested the translational value of targeting MG53 function in tissue repair and regenerative medicine using in vitro cell based assays and animal models. While native MG53 protein is restricted to striated muscle, beneficial effects against cellular injuries are present in non-muscle cells with overexpression of MG53. In addition to the intracellular action of MG53, acute injury of the cell membrane leads to exposure of lipid signals that can be detected by MG53, allowing recombinant MG53 to repair membrane damage when provided in the extracellular space. Human MG53 protein retains dose-dependent protection against membrane disruption in both muscle and non-muscle cells. Intravenous delivery of MG53 protein is safe in rodent models, with suitable pharmacokinetic properties that are highly effective in restoring or preventing localized damage to muscle tissues. Our data indicate the MG53 protein is an attractive biological reagent for restoration of membrane repair defects in human diseases.