Lipid Membrane Leaflets Unzip upon Hybridization with\nPolymer-Rich Nanodomains

There\nis a long-term interest in creating artificial biomimetic\nmembranes where self-assembled phospholipid bilayers are selectively\npermeabilized by synthetic channel-like molecules. One example is\nthe coassembly of amphiphilic block copolymers with phospholipids\ninto a hybrid membrane. Hybrid phospholipid block copolymer bilayers\ndisplay many properties, seen in biomembranes such as selective transport\nphenomena, synergistic elastic properties, and structural phase transformations.\nJust like in biomembranes, these fundamental properties of hybrid\nbilayers are often regulated by lateral phase separation. Understanding\nthe molecular and physical cues that determine the formation of rafts\nor domains in hybrid membranes, their size, and morphology is paramount\nto elucidating and programming their function. Employing a combination\nof coarse-grained molecular dynamics simulations and high-resolution\ncryogenic electron microscopy, we discovered that phosphatidylcholine-cholesterol\nbilayers hybridized with poly(butadiene-<i>b</i>-ethylene\noxide) develop two distinct phase-separated morphologies. At molar\nfractions of polymer above 10 mol % the expected molecular distribution\ninto lipid-rich and polymer-rich domains is observed. However, at\nlow polymer content, a new structure develops in which the bilayer\nleaflets unzip (but remain continuous) to incorporate nanodomains\nof hydrophobic butadiene globules. We conjecture that unzipping is\nenergetically more favorable than sustaining the hydrophobic mismatch\nbetween butadiene blocks and phospholipid acyl chains. These findings\noffer new insights into the morphology of biomembranes upon the insertion\nof transmembrane proteins with bulky hydrophobic residues.