Chiral tubule self-assembly from an achiral diynoic lipid

Abstract

Tubules possessing m-scale chiral substructure self-assemble from an achiral isomer of the tubule-forming diynoic phosphatidylcholine, 1,2-bis(10,12-tricosadiynoyl)sn-glycero-3-phosphocholine [DC(8,9)PC], showing that molecular chirality is not essential for tubule formation. CD spectroscopy shows that these structures' helical sense of handedness instead originates in a spontaneous cooperative chiral symmetry-breaking process. We conclude that the chiral symmetry-breaking must originate in the unusual feature common to the chiral and achiral tubule-forming molecules, the diynes centered in their hydrocarbon tails.T he chiral diynoic phosphatidylcholine 1,2-bis(10,12-tricosadiynoyl)sn-glycero-3-phosphocholine [DC(8,9)PC] (compound 1 of Fig. 1) self-assembles in ethanolic solutions to form microscopic (Ϸ0.5 m ϫ Ϸ30 m) hollow cylinders possessing an exterior helical trace similar to that found on a paper drinking straw. This trace is a remnant of the helical winding of a uniform-width phospholipid ribbon that forms tubules, and its helical sense of handedness is determined by the molecule's chirality: R-DC (8,9)PC form tubules possessing right-and left-handed exterior helical traces, respectively.The striking molecular chirality͞helical handedness correspondence has led to the idea that tubule formation is driven by molecular chirality. In the so-called ''chiral packing'' class of tubule formation and structure theories, the tubule-forming molecule's chiral shape causes the directors of neighboring molecules in the close-packed phospholipid bilayer membrane to be offset by a small angle. The cumulative effect of this director tilt is a helical twist along the membrane that results in the winding of the membrane to form closed cylinders. However, it has been recently shown that the L ␤Ј -phase helical ribbons that grow from enantiopure L ␣ -phase spherical vesicles are a nearly racemic mix of left-and right-handed helices (1). Minutes after the sphere-to-tubule transition is complete, lipid from the stillcooling DC(8,9)PC-saturated solution completely ensheaths the vesicle-derived helices through the coaxial helical growth of a second, outer cylinder. Paradoxically, whereas the core handedness ratio is nearly racemic, the outer cylinders have a uniform helical sense of handedness that corresponds to DC(8,9)PC chirality. Similar results have been obtained with two enantiomerically pure DC(8,9)PC analogs in which the phosphoryl oxygen linking the phosphatidylcholine headgroup to the chiral glycerol backbone has been removed or replaced by a methylene (-CH 2 -) group (2, 3). That three molecules possessing different chiral centers each produce nearly racemic helix handedness ratios suggests that the helices are not macroscopic expressions of molecular chirality. Instead, this apparently random membrane chiralization suggests a chiral symmetry-breaking mechanism that is a consequence of the L ␣ -to-L ␤Ј phase transition from which the helices form.Additional support for chiral symmetry-breaking models comes from studie...

Light-sensitive lipid-based nanoparticles for drug delivery: design principles and future considerations for biological applications

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Lipid Tubes with a Temperature‐Tunable Diameter

“…However, tubes can also be formed in racemic mixtures [8] or with achiral molecules. [15] In such cases, the chiral-symmetry-breaking model allows one to explain the formation of tubes. [14,16,17] This implies that both monolayers of the lipid membrane are not mirror images, which may occur for a tilted hexatic phase or if phase separation of the racemic mixture occurs.…”

Chiral structures from achiral liquid crystals in cylindrical capillaries

“…mirror symmetry | parity symmetry | topological defects | chiral defects T he emergence of chirality from achiral systems poses fundamental questions about which we have limited mechanistic understanding (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). When the chiral symmetry of an achiral system is broken, a handedness is established, and materials with different handedness commonly exhibit distinct and useful properties (10)(11)(12)(13)(14) relevant for applications ranging from chemical sensors (15,16) to photonics (17)(18)(19).…”

“…When the chiral symmetry of an achiral system is broken, a handedness is established, and materials with different handedness commonly exhibit distinct and useful properties (10)(11)(12)(13)(14) relevant for applications ranging from chemical sensors (15,16) to photonics (17)(18)(19). To date, considerable effort has been expended to control handedness in materials (for example, by chiral separation of racemic mixtures or chiral amplification of small enantiomeric imbalances) (1,8,(20)(21)(22). Recently and in a different vein, identification and elucidation of pathways by which achiral building blocks spontaneously organize to create chiral structures have become an area of active study.…”