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Multidimensional hierarchical self-assembly of amphiphilic cylindrical block comicelles

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Science  20 Mar 2015:
Vol. 347, Issue 6228, pp. 1329-1332
DOI: 10.1126/science.1261816

Cylindrical polymer micelles pack in 3D

When you control chemistry, solvents, temperature, and concentration, surfactants and block copolymers will readily assemble into micelles, rods, and other structures. Qiu et al. take this to new lengths through precise selection of longer polymer blocks that self-assemble through a crystallization process (see the Perspective by Lee et al.). They chose polymer blocks that were either hydrophobic or polar and used miscible solvents that were each ideal for only one of the blocks. Their triblock comicelles generated a wide variety of stable three-dimensional superstructures through side-by-side stacking and end-to-end intermicellar association.

Science, this issue p. 1329; see also p. 1310

Abstract

Self-assembly of molecular and block copolymer amphiphiles represents a well-established route to micelles with a wide variety of shapes and gel-like phases. We demonstrate an analogous process, but on a longer length scale, in which amphiphilic P-H-P and H-P-H cylindrical triblock comicelles with hydrophobic (H) or polar (P) segments that are monodisperse in length are able to self-assemble side by side or end to end in nonsolvents for the central or terminal segments, respectively. This allows the formation of cylindrical supermicelles and one-dimensional (1D) or 3D superstructures that persist in both solution and the solid state. These assemblies possess multiple levels of structural hierarchy in combination with existence on a multimicrometer-length scale, features that are generally only found in natural materials.

Amphiphiles such as molecular surfactants and block copolymers have been shown to form a rich variety of self-assembled nanoscopic structures, including spherical micelles, cylinders, nanotubes, bilayers, and vesicles as well as gel-like phases (1, 2). The construction of hierarchical colloidal materials on a longer length scale by use of spherical nanoparticles (3, 4), branched nanocrystals (5), nanorods (6), and nanocubes (7) has also recently been the subject of intense investigation. Control over the size, shape, and composition of these nanoscopic building blocks has enabled the formation of superstructures with substantial structural diversity (3, 7). Self-assembly of Janus and patchy nanoparticles formed by surface modification (8, 9) or from block copolymers (10), including diblock (11) and star (12) or linear triblock copolymers (1315), has further broadened the range of superstructures that can be prepared. Nevertheless, despite these impressive recent advances, the use of anisotropic amphiphilic building blocks derived from soft matter remains limited; examples include polymer-based (16) and polymer-metal hybrid nanorods (17, 18) and self-assembled nanotubes and cylinders (19, 20). These approaches represent the first steps toward the creation of tailored, functional hierarchical structures on the multimicrometer-length scale, a size domain currently dominated by biological assemblies.

We focused on the hierarchical self-assembly of amphiphilic cylindrical P-H-P triblock comicelles, as well as H-P-H triblock comicelles with an inverse sequence of the hydrophobic (H) and polar (P) segments. Their hierarchical self-assembly was controlled by means of solvent composition by using nonpolar hydrophobic hexane (or decane) and polar hydrophilic isopropanol (iPrOH). When added alone, these miscible solvents induce the stacking of the P or H segments, respectively. The triblock comicelles were prepared by means of living crystallization-driven self-assembly (CDSA) in a mixture of hexane and iPrOH (1:3 v/v), a medium in which the comicelles are individually dispersed. Block copolymers with a crystallizable poly(ferrocenyldimethylsilane) (PFS) core-forming block were used as precursors and possessed either a nonpolar, corona-forming H block [poly(dimethylsiloxane) (PDMS) or poly(methylvinylsiloxane) (PMVS)], or a complementary P block [poly(2-vinylpyridine) (P2VP)], to form the micelle periphery (Fig. 1 and fig. S1). The triblock comicelle building blocks were monodisperse in both the H and P segment lengths, a feature that is characteristic of the living CDSA method (2123).

Fig. 1 Formation of amphiphilic cylindrical P-H-P and H-P-H triblock comicelle building blocks via living CDSA.

(A) P-H-P triblock comicelles with a nonpolar, hydrophobic central segment (H) and two polar terminal segments (P) formed by the addition of PFS48-b-P2VP414 unimers to a solution of monodisperse cylindrical seed micelles of PFS49-b-PDMS504. (B) H-P-H triblock comicelles with an inverse sequence of the hydrophobic and polar segments formed by the addition of PFS49-b-PDMS504 unimers to a solution of monodisperse cylindrical seed micelles of PFS48-b-P2VP414. PDMS corona regions are not visible in the TEM image because of insufficient electron density contrast. The widths of the PFS cores are different for the H and P segments, which is often a feature of living CDSA processes that involve compositionally different block copolymer structures. The PFS core-forming block and the PDMS and P2VP corona-forming blocks are indicated by orange, red, and green colors, respectively.

Noncentrosymmetric H-H-P (24) and centrosymmetric P-H-P (25) amphiphilic triblock comicelles self-assemble in polar media to form spherical supermicelles of size 1 to 5 μm with various aggregation numbers. However, attempts to prepare cylindrical morphologies from P-H-P triblock comicelles by the use of a hydrophobic segment of increased length led only to poorly defined elongated structures (fig. S2). This is likely a result of the use of a terminal P segment with a large degree of polymerization (P2VP414), which generates a voluminous hydrophilic corona [overall diameter as observed with transmission electron microscopy (TEM) in dry state, ~70 nm (fig. S3A)] that disrupts the stacking of the hydrophobic segments through repulsive interactions (fig. S2C) (25). We envisaged that efficient side-by-side stacking of the central core-forming segment of the triblock comicelle is necessary to form well-defined and robust cylindrical structures. Two block copolymers with shorter P2VP blocks, PFS34-b-P2VP272 and PFS20-b-P2VP140, were therefore used. The resulting P-H-P triblock comicelles were shown by TEM to possess substantially smaller overall terminal P segment diameters (~40 nm and 20 nm in dry state, respectively) (fig. S3), indicating that the corresponding intermicellar steric interactions in supermicelle coronas should be appreciably reduced. Indeed, on formation of a polar colloidal solution (hexane, iPrOH 1:3 v/v) of the triblock comicelles P55 nm-H35 nm-P55 nm (Hh = PFS55-b-PMVS825 and Pp = PFS34-b-P2VP272; the subscripts “h” and “p” depict the segment length in nanometers) with a P segment of ~40 nm diameter, well-defined “train track–like” superstructures were observed by means of TEM after solvent evaporation due to side-by-side packing (Fig. 2A and fig. S4). The average separation between two parallel triblock comicelles as observed with TEM (corresponding to a low electron density and therefore an invisible region of coronal overlap for the H segments) was found to be ~44 nm, which is slightly larger than the overall diameter of the terminal segments (~40 nm). Longer P80 nm-H55 nm-P80 nm triblock comicelles with a slightly larger h/p ratio (0.69 versus 0.64) from the same block copolymer constituents were found to afford supermicelles with a significantly tighter packing (average separation, ~30 nm) (Fig. 2B). However, to increase the stacking interactions still further so as to create robust cylindrical architectures, we studied the self-assembly of P-H-P (P = PFS20-b-P2VP140) triblock comicelles with terminal P segments ~20 nm in diameter and various segment lengths and h/p ratios in iPrOH. This afforded a variety of well-defined supermicelles of length 1 to 10 μm with a cylindrical morphology (Fig. 2, C to E). Presumably with terminal P segments of even smaller diameter, the steric repulsions are further reduced, and the central H segments were very tightly stacked, as revealed by an apparent dark thread via TEM. The formation of persistent cylindrical supermicelles was confirmed by their existence in solution, as demonstrated with optical microscopy in iPrOH (Fig. 2, D and E, inset; fig. S5).

Fig. 2 1D supermicelles through side-by-side stacking of P-H-P triblock comicelles.

(A) TEM images of train track–like superstructures formed by P55 nm-H35 nm-P55 nm (H = PFS55-b-PMVS825, P = PFS34-b-P2VP272) triblock comicelles formed on drying from a mixture of hexane and iPrOH (1:3 v/v). (B) TEM images of supermicelles with a tighter parallel stacking of P80 nm-H55 nm-P80 nm (P = PFS34-b-P2VP272) triblock comicelles formed in iPrOH. (C) TEM images of a cylindrical brushlike supermicelle formed by P340 nm-H35 nm-P340 nm (P = PFS20-b-P2VP140) triblock comicelles in iPrOH. (D) TEM (left) and optical microscopy (right) images of cylindrical brushlike supermicelles formed by P560 nm-H35 nm-P560 nm (P = PFS20-b-P2VP140) triblock comicelles formed in iPrOH. (E) TEM and optical microscopy (inset) images of longer cylindrical supermicelles formed by P220 nm-H55 nm-P220 nm (P = PFS20-b-P2VP140) triblock comicelles in iPrOH. TEM analysis was performed after solvent evaporation. Optical microscopy characterization of the solutions was performed in sealed rectangular capillary tubes. Because of repulsions between the solvated coronas of the P sections, in solution the supermicelles in (C) to (E) likely take up a twisted structure in which the parallel stacking of the H sections is slightly compromised, rather than the 2D structure revealed by TEM in the dry state.

We also explored the formation of multidimensional superstructures by the intermicellar association of terminal segments using P-H-P triblock comicelles with spatially demanding ~70-nm-diameter P2VP414 coronas for the terminal P segments so as to favor intermicellar association. To trigger assembly, hexane or decane was rapidly added to a colloidal solution of the triblock comicelles (in 1:3 v/v hexane/iPrOH) so that the volume ratio of nonpolar to polar solvent reached 3:1 v/v.

When hexane was used, the end-to-end association yielded discrete superstructures. For the triblock comicelles with relatively short terminal P segments (p = 50 nm), the association predominantly gave irregular loops (for example, for P50 nm-H260 nm-P50 nm) (fig. S7). The terminal segments became fully overlapped at p > 100 nm, and the assembly was restricted to a single direction, favoring the formation of linear chainlike superstructures (for example, for P145 nm-H110 nm-P145 nm) (Fig. 3A and fig. S8A). Multiply stranded chains were formed by using more concentrated triblock comicelle solutions (fig. S8A), whereas single-stranded structures resulted when under dilute conditions (Fig. 3A). These chainlike superstructures can be readily made permanent through intermicellar cross-linking of the P2VP coronas of the interacting terminal segments, via coordination of the P2VP pyridyl groups with small Pt nanoparticles (Fig. 3B) (26, 27). The ends of the triblock comicelles also remained active toward living CDSA, as demonstrated by the addition of further unimer, enabling the subsequent growth of cylindrical micelle brushes (fig. S10).

Fig. 3 Multidimensional superstructures through end-to-end stacking of P-H-P triblock comicelles.

(A) TEM images of mainly single-stranded chains formed by the addition of hexane to a diluted solution (molar concentration = 1/6 original concentration, C0; details are provided in the supplementary materials) of P145 nm-H110 nm-P145 nm (H = PFS49-b-PDMS504, P = PFS48-b-P2VP414) triblock comicelles in 1:3 (v/v) hexane/iPrOH. (B) TEM images of an immobilized chain formed by intermicellar cross-linking of P2VP coronas of stacked terminal segments. (C) TEM image of an irregular network formed by the addition of decane to a solution (concentration = C0) of P50 nm-H190 nm-P50 nm triblock comicelles in 1:3 (v/v) hexane/iPrOH. (D) Optical microscopy (top left) and TEM (bottom left and right) images of chain networks formed by the addition of decane to a diluted solution (concentration = 1/10 C0) of P145 nm-H110 nm-P145 nm triblock comicelles in 1:3 (v/v) hexane/iPrOH.

The degree of end-to-end association dramatically increased when decane was used as the nonpolar solvent. This led to an additional level of hierarchical self-assembly, yielding large superstructures that extended in more than one dimension. For example, the triblock comicelles with short terminal segments (p = 50 nm) formed irregular multidimensional architectures in decane [for example, for P50 nm-H190 nm-P50 nm (Fig. 3C) and P50 nm-H110 nm-P50 nm (fig. S11)], in which the end-to-end association was random in direction, giving superstructures composed of cross looplike units. In contrast, the association of micelles with longer terminal segments (such as P145 nm-H110 nm-P145 nm) produced disordered superstructures in more concentrated solutions (fig. S8B) but large and continuous networks of chains, with long, multiply stranded subunits connected by “bridging” micelle chains in dilute solution (Fig. 3D and fig. S12).

In previous studies (25), the nonpolar central H segments of P-H-P triblock comicelles stacked crosswise during the self-assembly in polar media to form spherical supermicelles (fig. S2, A and B). This type of organization for terminal H segments yields higher-dimensional assemblies. For example, we found that H-P-H triblock comicelle cylinders (P = PFS48-b-P2VP414, H = PFS49-b-PDMS504) self-assemble into a variety of multidimensional superlattices in iPrOH (for Hh-P160 nm-Hh, where h = 70, 105, 250, or 410 nm) (Fig. 4 and fig. S13). When the terminal segments were relatively short (such as h = 105 nm), the H-P-H triblock comicelles preferred to form regular 3D superstructures. TEM analysis revealed dark (electron-dense) regions derived from intermicellar association of the H segments and lighter regions with relatively loosely bundled central P segments (Fig. 4A and fig. S13B). TEM images acquired in a thinner region of the sample showed that the darker dots formed an array with a d-spacing of ~310 nm (Fig. 4A). Further insight into the organization of the triblock comicelles in the superlattices was revealed through structural reconstruction based on electron tomography (Fig. 4B, fig. S14, and movie S1). The darker areas consisting of cross-stacked terminal H segments were woven together by the central P segments across several layers. As the length of the terminal segments was increased, the three-dimensional (3D) superlattices started to deform, and the darker regions began to fuse into strips (for example, for h = 250 nm) (fig. S13C). In contrast, 1D superstructures formed as the length of the terminal H segments was increased to above 400 nm (for example, h = 410 nm) (Fig. 4C and fig. S13D), and the triblock comicelles aligned in a parallel fashion, forming periodically segmented 1D columnlike structures. Analogous experiments for triblock comicelle cylinders with a longer central segment (p = 325 nm) revealed similar 3D to 1D structural changes, with an increase in the length of the terminal segments (h ≤ 350 nm for 3D and h ≥ 550 nm for 1D superlattices) (fig. S15). In this case, values of h/p < ~1 favored 3D assemblies, whereas h/p ratios > ~1.5 led to a preference for 1D superstructures (table S4).

Fig. 4 3D and 1D superlattices through end-to-end stacking of H-P-H triblock comicelles.

(A) TEM images of a 3D superlattice formed by H105 nm-P160 nm-H105 nm (P = PFS48-b-P2VP414, H = PFS49-b-PDMS504) triblock comicelles. (B) A 3D superlattice revealed with electron tomography and 3D structural reconstruction. (C) TEM image of a 1D superlattice formed by H410 nm-P160 nm-H410 nm triblock comicelles. (D) Preparation of fluorescent (H/HG)-P-(H/HG) triblock comicelles and CLSM image of (H/HG)300 nm-P570 nm-(H/HG)300 nm triblock comicelles. The fluorescent corona-forming block of PFS62-b-(PDMS605-r-G21) is indicated in bright green. (E) CLSM images of a 3D superlattice formed by (H/HG)300 nm-P570 nm-(H/HG)300 nm triblock comicelles in iPrOH. (F) CLSM images of a 1D superlattice formed by (H/HG)745 nm-P570 nm-(H/HG)745 nm triblock comicelles in iPrOH.

To enable direct characterization of the superlattices in solution, green fluorescent dye–labeled PFS62-b-(PDMS605-r-G21) (28) was blended with PFS49-b-PDMS504 to form fluorescent hydrophobic terminal segments, H/HG (Fig. 4D and fig. S1). The resulting (H/HG)h-Pp-(H/HG)h (H/HG = 3:1 by mass) triblock comicelles were readily visualized in solution by means of confocal laser scanning microscopy (CLSM) (Fig. 4D). Because of the resolution limits of CLSM (fig. S16), we focused on the superlattices formed by the triblock comicelles with longer central segments (p = 570 nm) (Fig. 4D and figs. S17 and S19). CLSM images (Fig. 4, E and F; figs. S18 and S19; and movie S2) clearly showed that the (H/HG)300 nm-P570 nm-(H/HG)300 nm triblock comicelles with h/p ~ 0.5 formed 3D superlattices, whereas the (H/HG)745 nm-P570 nm-(H/HG)745 nm triblock comicelles, with longer terminal segments and h/p ~ 1.3, formed segmented 1D superstructures. It was also apparent that in several domains of the 3D superlattices, the fluorescent dots were arranged in a psuedorectangular lattice with repeat spacing of ~760 nm (Fig. 4E, inset). The use of triblock comicelles with either green- or red fluorescent dye–labeled central hydrophobic segments (H/HG or H/HR) also provided evidence for the lack of micelle building block exchange in solution for both cylindrical supermicelles (fig. S6) and 1D chainlike superstructures (fig. S9) over 7 days at 22°C. This indicated that the assemblies formed should be regarded as kinetically trapped rather than equilibrium structures.

Amphiphilic cylindrical triblock comicelles afford a wide variety of superstructures through side-by-side stacking and end-to-end intermicellar association (tables S1, S3, and S4). The process is readily controlled by altering the comicelle architecture in terms of the sequence, chemistries, lengths, and diameters of the various segments, as well as the nature of the solvent used. Despite the observation that the self-assembled materials are not formed under equilibrium conditions, the spherical and cylindrical morphologies generated by side-by-side assembly can be qualitatively rationalized through trends in the critical packing parameter, a concept developed for molecular surfactants (table S2). The formation of 1D or 3D superlattices by means of end-to-end assembly is related to the h/p ratio where a larger value favors parallel (1D) stacking (table S4). The coronal blocks can be readily functionalized (as illustrated with fluorescent dyes) and cross-linked; moreover, the CDSA method is applicable to a variety of crystallizable block copolymers and related species (28, 29), including those based on semiconducting (2, 30) and biodegradable materials (31). The approach described therefore offers opportunities to develop functional and robust micrometer-scale assemblies with potential applications in areas such as sensing and biomedicine and also in optoelectronics and as photonic crystals.

Supplementary Materials

www.sciencemag.org/content/347/6228/1329/suppl/DC1

Materials and Methods

Figs. S1 to S19

Movies S1 and S2

References (3237)

References and Notes

  1. Acknowledgments: H.Q. acknowledges the European Union (EU) for a Marie Curie Postdoctoral Fellowship and the European Research Council (ERC) for a Postdoctoral Fellowship. Z.M.H. is grateful to the EU for a Marie Curie Postdoctoral Fellowship. I.M. thanks the EU for an ERC Advanced Investigator Grant. M.A.W. thanks the Natural Sciences and Engineering Research Council of Canada for financial support. The authors also thank J. Mantell and A. Leard (Wolfson Bioimaging Facility, University of Bristol) for TEM, CLSM, and optical microscopy imaging and tomography analysis. H.Q. and I.M. conceived the project, and H.Q. performed the experiments. Z.M.H. prepared the fluorescent PFS block copolymers. H.Q., Z.M.H, and I.M. prepared the manuscript with input from M.A.W. The project was supervised by I.M., with input from M.A.W.
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