Figure 21.1 One inspiration for synthetic polymer membranes and rods: cell crawling. Outlines of a cell traced from images of an actin-labeled cell crawling on an adhesive surface (inset). The cell’s plasma membrane and inner nuclear (double) membrane are both displaced from left to right over a period of ~1 min. Forward movement occurs primarily by polymerization of stiff actin filaments which are selectively shown as black rods or as dense gray regions. Polymerization is faster at the biased, (+)-ends of filaments. Anchoring of the opposite ends of the filaments extends through the membrane in cell adhesion to the substrate. Because the filaments are stiff, filament polymerization drives the membrane forward. Because the cell membrane is robust, it can be torn away from the substrate at the rear of the cell. (From Ref. 14 by permission of Elsevier Science.)

Figure 21.2 Schematics of molecular shapes which arise in hydration of the polar chains of amphiphiles. Such shapes underlie the formation of various morphological phases: vesicles, worms, and spheres. Vesicles predominate when the polar fraction, f, of most simple amphiphiles is in the indicated range. Polyethyleneoxide (PEO) is a typical, non-ionized polar chain with a high oxygen content (red atoms) that facilitates hydration. The hydrocarbon segments of the amphiphiles interact with each other, driving aggregation and excluding water to create a hydrophobic core. A vesicle is sketched with a small section removed to reveal the core’s nano-scale thickness d. Rod-like worm micelles form when the polar segments are made slightly longer, while spheres form for even longer polar segments. (From Ref. 14 by permission of Elsevier Science.)

Figure 21.3 Synthetic polymer membranes and worms made by self-assembly of PEO-based diblocks in water. The weight or volume fraction of the hydrophilic PEO (polyethylene oxide) block is specified by f. The hydrophobic, hydrocarbon block of the copolymers thus far studied consists of either PEE (polyethylethylene) or its crosslinkable analog PBD (polybutadiene). Note that an increased f by just a few percent leads to worm micelles instead of vesicles. Cryo-TEM has already shown that the worm micelles, made of block copolymers of molecular weight MW ~ 4 kDa, have hydrophobic cores of ~10 nm.

Figure 21.4 Polymersome membrane structure scheme, vesicle formation, and intrinsic membrane property trends. (A) Schematic of a polymersome membrane series (plus lipid) made from increasing molecular weight copolymers. The hydrophobic core thickness is d. (B) Analogous to liposomes, diblock copolymer vesicles can be formed by hydration of a thin, dried film of copolymer. Aqueous solutions can vary from phospate-buffered saline to 1 M sucrose or distilled water. (C) Schematic of membrane properties versus amphiphile molecular weight based on single vesicle measurements and ranging from liposomes to polymersomes, with n.a. denoting non-aggregating systems. Liposomes and related vesicles are generally made with amphipiles with MW less than 1 kDa; polymersomes can be made in aqueous solution with larger amphiphiles. Difficulties at high MW might be attributed to a rapid decrease in fluidity associated with entangling chains. At least for strongly segregating diblocks, the membrane thickness increases with MW, and makes polymersomes decreasingly permeable. Stability by a number of measures also increases, but only up to a limit set by the interfacial tension that arises with membrane formation.

Figure 21.5 Point-attached worm micelles under flow. (A) Trumpet envelopes of conformations exhibited by non- crosslinked worms. The mean flow velocity is indicated; higher velocities narrow the trumpets. Lack of worm fragmentation under all such flows is consistent with strongly associated systems. (B) Configuration envelope of a crosslinked worm under flow. Note the persistent kink which resists straightening under flow. (From Ref. 14 by permission of Elsevier Science.)

Figure 21.6 Polymer amphiphile systems at the interface with biology. (A) Virus-assisted loading of a triblock copolymer vesicle containing a natural channel protein in its membrane (From Ref. 51 by permission of the National Academy of Sciences.); for liposomes, see Lambert et al.[i] (B) Protein-polymer hybrid amphiphile which assembles in a THF/Water solution into rod-like micelles. (From Ref. 52 by permission of the American Chemical Society.) (C) Biocompatibility studies of PEO based polymersomes. 6,54 The exponential decay in circulating polymersomes in a rat model indicates a circulation half-life very comparable to times found for stealth liposomes. 42 The inset below the curve is a cryo-TEM image of ~100 nm (scale bar) polymersomes. The two optical micrographs at right show giant polymersomes, P, placed in contact with a phagocytic neutrophil, N by a micropipette (of diameter 5 µm). R denotes a red blood cell. The vesicles have been pre-incubated in plasma for the indicated times and only after tens of hours are the polymersomes engulfed by the phagocytic neutrophils. (From Ref. 42 by permission of Elsevier Science.)[i]