Collapse of Lipid Membranes into Distended Lipidic Cubic Phases at High Solvent Levels, Membrane Remodelling, and...

Performance plastics, such as poly(methyl methacrylate), underpin the modern economy. Global manufacturing of plastic precursors relies on fossil carbon sources, and the urgently needed shift toward renewable carbon use through biofermentation is hindered by the low tolerance of producer strains to methacrylate esters. The principal mode of butyl methacrylate cellular toxicity is membrane disruption. To understand this process, the conditions for membrane stability, and recovery after solvent shock, we investigate the phase stability of hydrated lipid membranes at high levels of a key intermediate, butyl methacrylate. We assess the role of cis- vs trans-unsaturation in 18-carbon chain phospholipids on butyl methacrylate-induced phase conversion and polymorphism. Using ssNMR, SAXS and cryoEM, we demonstrate the formation of stable lipidic cubic phases in hydrated lipid/solvent (cis-chain phospholipid lipid/butyl methacrylate) systems at a 1:6 molar ratio entirely lacking monoolein. Transient lipidic cubic phases form in trans-chain phospholipid/butyl methacrylate systems, which slowly convert to bilayers through a spontaneous "membrane healing" process during recovery after solvent shock. The observed bicontinuous nanostructures with a cubic phase architecture coexist with a stable, monocontinuous hydrated phase of the same morphology but with simpler topological connectivity, which demonstrates that phase stability in cubic phases does not require topological complementarity. We propose trans-lipid substitutions in membranes of fermentative strains as a key step toward sustainable production of methacrylate esters.