Membrane proteins are involved in nearly all cellular processes, including energy production and signaling. Altered membrane protein activity can disrupt vital cellular processes, resulting in diseases such as cancer. Membrane proteins are the most common targets for disease treatment, but structural and functional studies are challenging for membrane proteins because their activity and solubility is limited outside of a native lipid bilayer. Nanodiscs are emerging as the preferred system for studying membrane proteins. Offering precise control over particle size and composition, Nanodiscs consist of a phospholipid bilayer stabilized by membrane scaffold proteins. We have developed a microfluidic system for assembly and purification of Nanodiscs that offers the same quality of Nanodiscs as bulk scale methods, but our method requires a fraction of the time and consumes much less precious membrane protein material. Nanodisc libraries can be made with whole cell lysate as the starting material for Nanodisc assembly, and these libraries have been shown to accurately represent native membrane protein composition. Using our microfluidic platform, we have generated Nanodisc libraries from patient-derived xenografts of glioma tumors and use these libraries to perform functional screening of membrane proteins. Membrane protein function of tumor-derived Nanodisc libraries could serve as a vital tool to select targeted therapeutics for cancer treatments by providing a direct measurement of the functional activity of key drivers of tumor progression.<br/>

Functional screening of membrane proteins with microfluidic nanodisc libraries

254th National Meeting (2017)

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