Will a Carbon Nanosheet serve as a replacement to membrane components in a Nanodisc?

Nanodisc is a nano size architecture of an intrinsic biological membrane protein. This in vitro nano biological science process is rapidly evolved into a technology that produce solubilized membrane proteins in their native... [ view full abstract ]

Nanodisc is a nano size architecture of an intrinsic biological membrane protein. This in vitro nano biological science process is rapidly evolved into a technology that produce solubilized membrane proteins in their native environment for biomedical and drug discovery applications. The organization of nanodiscs involve a protein enclosed phospholipid bilayer system held together by membrane scaffold proteins (MSPs). MSPs are condensed forms of apolipoprotein (apo) A-I which wrap around a patch of a lipid bilayer to form a disc-like particle or nanodisc. MSPs basically act as a ribbon/sheet to tie the lipid assembly, and simultaneously provide aqueous solubility for the system. Therefore, several engineered MSPs are designed and evaluated by reconstitution. Typically, the MSPs are produced by using recombinant technology and protein purification. To simplify the process, we are interested in designing simple organic structures as substitute for the total membrane components that include both MSPs and lipid layer. As an initiative we attempted a molecular modelling study to assess the propensity of a carbon nanosheet as supporting membrane structure for the protein to form a nanodisc. In this process, we identified a bacterial outer membrane protein porin as example structure to model the carbon nanosheet variant of its nanodisc (Fig 1.). A molecular dynamics study was performed to compare the binding interactions and conformational stability between the native nanodisc model of porin and the nanosheet variant. The nanosheet protein variant was found to be stable and offered a strong hydrophobic interaction network for the protein assembly. Our preliminary study results are interesting and strongly support our idea of nanosheet frame work as substitute for biological membrane system in current nanodisc technology. We anticipate that the carbon nanosheet with its native hydrophobic design and proven flexibility in surface chemical modification, shall be a good alternate for MSPs and could bring new horizons in nanodisc technology.

Acknowledgements: NRF-KIC Travel grant, UKZN-College of Health Sciences, UKZN-Nanotechnology Platform and CHPC Capetwon, South Africa.