Direct observation of defects and increased ion permeability of a membrane induced by structurally disordered Cu/Zn-superoxide dismutase aggregates.
Interactions between protein aggregates and a cellular membrane have been strongly implicated in many protein conformational diseases. However, such interactions for the case of Cu/Zn superoxide dismutase (SOD1) protein, which is related to fatal neurodegenerative disorder amyotrophic lateral sclerosis (ALS), have not been explored yet. For the first time, we report the direct observation of defect formation and increased ion permeability of a membrane induced by SOD1 aggregates using a supported lipid bilayer and membrane patches of human embryonic kidney cells as model membranes. We observed that aggregated SOD1 significantly induced the formation of defects within lipid membranes and caused the perturbation of membrane permeability, based on surface plasmon resonance spectroscopy, atomic force microscopy and electrophysiology. In the case of apo SOD1 with an unfolded structure, we found that it bound to the lipid membrane surface and slightly perturbed membrane permeability, compared to other folded proteins (holo SOD1 and bovine serum albumin). The changes in membrane integrity and permeability were found to be strongly dependent on the type of proteins and the amount of aggregates present. We expect that the findings presented herein will advance our understanding of the pathway by which structurally disordered SOD1 aggregates exert toxicity in vivo.
School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, Republic of Korea.
Inhee
I
Choi
Hyeon Don
HD
Song
Suseung
S
Lee
Young In
YI
Yang
Joo Hyun
JH
Nam
Sung Joon
SJ
Kim
Jung-Joon
JJ
Sung
Taewook
T
Kang
Jongheop
J
Yi
D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D008567:Membranes, Artificial; D018625:Microscopy, Atomic Force; D010539:Permeability; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism*; D020349:Surface Plasmon Resonance
D008567:Membranes, Artificial; D013482:Superoxide Dismutase