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Polymer-based lipid nanoparticles like styrene-maleic acid lipid particles have revolutionized the study of membrane proteins. More recently, alternative polymers such as poly(diisobutylene- al -maleic acid) (DIBMA) have been used in this field. DIBMA is commonly synthesized via conventional radical copolymerization. In order to study the influence of its chain length on lipid nanodisc formation and membrane protein extraction, we synthesized DIBMA with molar masses varying from 1.2-12 kDa via RAFT-mediated polymerization. For molar masses in the range of 3-7 kDa, the rate of lipid nanodisc formation was the highest and similar to those of poly(styrene- co- maleic acid) (SMA) and commercially available DIBMA. ZipA solubilization efficiency was significantly higher than for commercially available DIBMA and similar to SMA (circa 75%). Furthermore, RAFT-made DIBMA with a molar mass of 1.2-3.9 kDa showed a much cleaner separation on SDS-PAGE, without the smearing that is typically seen for SMA and commercially available DIBMA.

Influence of DIBMA Polymer Length on Lipid Nanodisc Formation and Membrane Protein Extraction