Multilayered Polymersome Formed by Amphiphilic Asymmetric

Article pubs.acs.org/Macromolecules

Multilayered Polymersome Formed by Amphiphilic Asymmetric Macromolecular Brushes Hung-Yu Chang, Yung-Lung Lin, and Yu-Jane Sheng* Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan 106, R.O.C

Heng-Kwong Tsao* Department of Chemical and Materials Engineering, Department of Physics, National Central University, Jhongli, Taiwan 320, R.O.C ABSTRACT: Well-defined amphiphilic asymmetric macromolecular brushes were synthesized recently and were able to self-assemble into vesicles in selective solvents. The self-assembly of polymer brushes consisting of a solvophobic backbone attached with two different side chains, solvophilic and amphiphilic diblock, is explored by dissipative particle dynamics. Dependent on the block length, molecular architecture, and grafting density, the multicompartment aggregate exhibits a rich variety of morphological conformations, including five types of vesicles: porous aggregates, worm-like micelles, donut micelles, hamburger micelles, and unimolecular micelles. For certain polymer brushes, atypical polymersomes with asymmetric multilayered membranes are spontaneously formed. In addition, temperature variation induced morphological transformation from an asymmetric four-layered polymersome to a symmetric seven-layered polymersome is observed for polymer brushes containing a thermoresponsive block. Consequently, the resulting polymersome decreases in size quite sharply as temperature exceeds lower critical solution temperature. These simulation findings are consistent with experimental observations. By varying the lengths of various blocks, the morphological phase diagram and internal structures of the resulting aggregates are obtained. At a fixed composition of polymer brushes, the aggregate morphology varies with the structural arrangement of the two solvophilic blocks in the molecule. Asymmetric polymersomes are formed when the two solvophilic blocks are separately attached to the backbone and side chain. Although asymmetric vesicles are observed at moderate grafting density, unique donut aggregates are formed for high density but hamburger micelles develop at low density.

I. INTRODUCTION Nanostructural copolymers with different macromolecular architecture are of increasing interest in recent years due to their distinctive physical properties.1 Linear multiblock, comblike, star-like, dendritic, hyperbranched, and brush-like polymers are all with different topological structures. For example, dendrimers are macromolecules with tree-like architectures and are typically symmetric around the core, adopting a spherical three-dimensional morphology.2,3 Starshaped copolymers also exhibit distinct aggregative behaviors from those of their linear counterparts. It is possible for them to form unimolecular micelles by increasing the arm number or the soluble block length.4,5 Because of the unique physical characteristics, such as monodispersity and encapsulation ability, supramolecular entities formed by dendrimers and star-shaped copolymers have been explored for the encapsulation of hydrophobic compounds as drug delivery vehicles. © 2012 American Chemical Society

New types of copolymers with branched and hyperbranched architectures have also been developed due to the progress in controlling polymerization processes.6−9 Grafted copolymers are a special type of branched copolymer in which the side chains are structurally distinct from the main chain. Graft copolymerization is an attractive method to impart a variety of functional groups to a polymer. When the density of the tethered side chains starts to affect the flexibility of the backbone of the copolymer, grafted polymers transform into brush polymers.10 The brush polymers generally adopt a wormlike cylindrical conformation since the densely crowded side chains are stretched away from the backbone because of the excluded volume effect.11 Three types of multicomponent copolymer brushes were proposed, i.e., double-cylinder type, Received: April 10, 2012 Revised: May 6, 2012 Published: May 15, 2012 4778

dx.doi.org/10.1021/ma3007366 | Macromolecules 2012, 45, 4778−4789

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prototype, and block type.12 Each type has its unique structure which may exhibit distinctive properties. One special type of brush polymer, i.e., polymers with two different side chains on each repeating unit of the backbone, emerged in recent years.11,13,14 This type of polymer is called asymmetric macromolecular brushes. Since the constituent blocks may possess different degree of solvophobicity, these polymer brushes can exhibit amphiphilic properties and form self-assembled nanostructures. For example, several amphiphilic asymmetric macromolecular brushes were found to be able to self-assemble into micelles and vesicles in selective solvents.11,13−15 However, these studies are still at an initial exploratory stage into the issue. Because of the complicated and confined structures, amphiphilic asymmetric macromolecular brushes possess the additional complexity in the self-assembly behaviors. Detailed investigations about the effect of architecture on the resulting aggregative morphologies, and characteristic properties are still needed. This information is of great importance for the understanding of the connection between structure and properties and for the design of new nanomaterials. The experiments of Lian et al.11 served as a reference point for the parametrization of the model studied in this work. An amphiphilic asymmetric macromolecular brush, bearing PEO and PS-b-PNIPAM side chains on PGMA backbone by multiple synthesized approaches, was produced. PNIPAM is a thermoresponsive polymer with its lower critical solution temperature (LCST) at 32 °C. PNIPAM becomes less soluble (more solvophobic) in water at elevated temperatures. It was found that the macromolecular brushes can self-assemble into vesicular structure in an aqueous solution. Also, temperature exerted a significant effect on the morphology of the structures. At a temperature above LCST of PNIPAM, the size of the vesicles decreased due to the shrinking of PNIPAM blocks in the corona. Lian and the co-workers also found that asymmetric macromolecular brushes with only PEO and PS side chains, i.e., without PNIPAM block, self-assembled into vesicle structures in methanol.11 PS side chains were in the walls of the vesicles, and PEO side chains were in the coronae. Obviously, the selfassembled aggregates of polymer brushes can be manipulated by adjusting specific polymer properties such as the arrangement of blocks and the chemical nature of the repeat unit. Nevertheless, there are still many questions remaining unanswered. For example, what is the effect of specific molecular architecture on the aggregative properties? Will the self-assembled behaviors of the polymer brushes be affected by their grafting density? How will the overall morphology and internal structure change for polymer brushes with different relative block lengths? Experimental studies of the self-assembly behaviors of macromolecular brushes are restricted owing to the synthetic difficulties of well-defined brush polymers with specific architectural configurations and controlled molecular weights. The theoretical approach based on molecular simulation may provide valuable microscopic insights and complement the deficiency of experimental studies on the self-assembly behavior of macromolecular brushes. Mesoscopic simulations, such as dissipative particle dynamics (DPD), allow in silico experiments to be easily and inexpensively performed on complex, soft materials. Furthermore, DPD simulation is currently the only viable simulation method that can be employed to study important macromolecular morphological expressions on the relevant length and time scales. It has been successfully applied

to explore a wide variety of complex phenomena such as micellization−demicellization process and micellar shuttle of a diblock copolymer in a biphasic system,16 polymer-protected nanoparticle self-assembly,17 and self-assembly behaviors of rod−coil block copolymers.18,19 Also, Liu and co-workers observed vesicle formation and fusion for comb-like block copolymers.20 Zhong and Liu found muicompartment micelles by varying block length in a systematic way.21 Lin and coworkers investigated the aspect ratio effect on the selfassembled structure of nanoplatelet and nanorod.22 The success in these studies indicates that DPD simulation is a very promising tool to study the self-assembly behaviors of amphiphilic asymmetric macromolecular brushes. As a consequence, the main objective of the current work is to achieve a qualitative understanding of the effects of block length, molecular architecture, and grafting density on the morphological outcomes of the self-assembled amphiphilic asymmetric macromolecular brushes by employing DPD.

II. MODEL AND SIMULATION METHOD The dissipative particle dynamics (DPD) is a particle-based mesoscale simulation technique that explicitly includes solvents and reproduces hydrodynamic behavior. Introduced by Hoogerbrugge and Koelman in 1992,23 the DPD method combines some of the detailed description of molecular dynamics, and thus DPD beads obey Newton’s equation of motion24,25 dri = vi, dt

dvi = fi/mi dt

(1)

where ri is the position vector, vi is the velocity vector, mi is the mass of beads, and fi denotes the total forces acting on bead i with mass mi. These DPD beads are subject to soft potentials and governed by predefined collision rules. As a result, this mesoscale method allows the simulation of hydrodynamic behavior in much larger, complex systems, up to the microsecond range. A. Interactions between DPD Beads. The force fij exerted on bead i by bead j is composed of a conservative force (FCij ), a dissipative force (FDij ), and a random force (FRij ). Thus, the total force acting on bead i is given by fi =

∑ (FCij + FijD + FijR ) (2)

j≠i

The sum acts over all beads within a cutoff radius rc beyond which the forces are neglected. These forces conserve net momentum and all act along the line joining two interacting particles. The conservative force FC for nonbonded beads is represented by a soft-repulsive interaction FCij = aij(rc − rij)riĵ ,

rij ≤ rc ; 0, rij > rc

(3)

where aij is a maximum repulsion between particles i and j. rij denotes the distance between the two beads, and r̂ij is the unit vector joining beads i and j. The dissipative force is proportional to the relative velocity, vij = vi − vj FijD = −γw D(rij)(riĵ ·vij)riĵ

where γ is the coefficient controlling the magnitude of the dissipative force and wD is a r-dependent weight function. The random force denotes the thermal motion of unresolved scales, such as the molecules inside each particle 4779


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Figure 1. Schematic diagrams of the realistic PGMA-graf t-(PEO/PS-b-PNIPAM) and its corresponding model polymer brush, Y15-graft-(Rx/By-bGz).

FijR = −σw R (rij)θij riĵ

represented by the yellow bead, B by the blue bead, R by the red bead, and G by the green bead. The mapping between the macromolecular brushes and the coarse-grained Y15-graf t-(Rx/ By-b-Gz) polymer in our DPD simulations can be performed as follows. First, an isolated macromolecular brush PGMA-graf t(PEO/PS-b-PNIPAM) was constructed by using Materials Studio’s polymer and simulation modeling software.26 It was found that the four repeat units of PS, PEO, and PNIPAM can be taken as a spherical bead with diameter equal to 10 Å . The water molecule has the size of ∼1.51 Å, and therefore one DPD bead contains roughly seven water molecules. Figure 1 demonstrates how PGMA-graf t-(PEO/PS-b-PNIPAM) is mapped onto the model polymer brush. In our model, the total number of beads for the backbone is 15 and the backbone is grafted at one bead interval in most of the cases. However, polymer brushes with backbones grafted at different intervals are also considered to investigate the effect of grafting density on the polymers′ self-assembled morphologies. On the basis of the models of the interaction and polymer brush described above, the dynamics of 192 000 DPD particles was performed in a cubic box (403) under periodic boundary conditions. The system density is set to 3. Note that in DPD simulations all the units are scaled by the bead mass m, cutoff distance rc, and thermal energy kBT. The equation of motion is integrated with a modified velocity Verlet algorithm24 with λ = 0.65 and Δt = 0.04. Since DPD simulation utilizes soft-repulsive potentials, the systems studied are allowed to evolve much faster than the “brute-force” molecular dynamics. Therefore, a typical DPD simulation requires only about 105 steps to equilibrate. In this work, each simulation takes at least 1 × 106 steps and the first 3 × 105 steps are for equilibration. Also, we have performed the simulations with different initial random configurations and for various box sizes. The resulting structures are reproducible, and therefore it is believed that these structures are at equilibrium.

where σ = (2γkBT)1/2 represents the noise amplitude, wR is a rdependent weight function, and θij is a randomly fluctuating variable whose average number is zero. The dissipative force acts to reduce the relative momentum between beads i and j, while random force is to impel energy into the system. For applying DPD to our brush polymer system, two addition bonding forces are adopted. The spring force (FSij) is to bind together the connected beads of the polymer brush FSij = − ∑ C S(rij − req)riĵ (4)

j S

where C is the spring constant and req denotes the equilibrium bond length. In order to properly represent the slightly stretched conformation caused by the bulkiness of the side chains, the angle spring force (FSθ ij ) is added to the backbone θ FSi θ = − ∑ C θ(rij − req )riĵ j

As a result, the stiffness of the backbone is tuned by the spring force between the first and third beads in every three neighboring beads. This force tends to compel the bond angle between two consecutive bonds to be close to the value of π. We have chosen CS = Cθ = 100, req = 0.7, and rθeq = 2req = 1.4. These choices of CS and req will not affect the qualitative behavior of the systems studied in this work. B. System Parameters. In this study, we consider the amphiphilic asymmetric macromolecular brush synthesized by Lian et al.11 To mimic the macromolecular brushes (PGMAgraf t-(PEO/PS-b-PNIPAM)) qualitatively, a model polymer brush Y15-graf t-(Rx/By-b-Gz) is proposed, as shown in Figure 1. Therefore, in our system, there are five different species of DPD beads which are solvent (S), two kinds of solvophobic beads (Y and B), and two solvophilic beads (R and G). Note that Y is 4780


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interaction parameter can be estimated from the Flory− Huggins χ-parameter by their χ−a relation: χij = (0.286 ± 0.002)(aij − aii), where aii = 25 for i = Y, B, R, G, and S. “Blends”, which is the module of Materials Studio from Accelrys Inc., provides a way to acquire χ by estimating the miscibility behavior of binary mixtures.26 It predicts the thermodynamics of mixing directly from the chemical structures of the five kinds of beads and, therefore, requires only their molecular structures and a force field as inputs. Here, the COMPASS force field is used. The χ parameters estimated from the Blends module are also shown in Table 1, and the interaction parameters can then be calculated by the χ−a relation. Note that the interaction parameters are rounded to “cleaner” numbers. Nevertheless, the simulation outcomes should remain qualitatively unaffected. Compared to all-atom simulations, the DPD approach seems to be less refined. Nevertheless, our intention is to develop a coarse-grained model that possesses characteristic physical and structural features of solvent and macromolecular brush system.

The concentration of model polymer brush in the solution (φp) is defined as φp =

nbrushlbrush total beads of polymer = total beads in the system nbrushlbrush + nsol

where nsol is number of solvent beads, nbrush is the number of polymer brushes in the system, and lbrush is the total number of beads associated with a polymer brush, lbrush = (15 + x + y + z). φp is set to be 0.05 in most cases. The interaction parameters chosen are shown in Table 1. These repulsive interaction parameters (aij) used in this work Table 1. Interactions Parameters (aij) for the Y-graf t-(R/Bb-G) in Aqueous Solutiona aij(χij)

S

S Y R B G

25

Y (backbone) solvophobic

R (side-chain) solvophilic

B (block) solvophobic

G (block) solvophilic

50 (9.7) 25

25 (0.3) 50 (9.5) 25

45 (6.0) 50 (10.2) 50 (6.9) 25

15−50 50 (10.6) 26 (2.6) 26 (0.3) 25

III. RESULTS AND DISCUSSION In this study, dissipative particle dynamics is applied to investigate the morphological conformations of the amphiphilic asymmetric macromolecular brushes in selective solvents. First, comparisons between the experimental findings and our simulation results are presented to illustrate the validity of our model polymer brush and simulation approach. Atypical multilayered polymersomes are observed and the detailed morphological changes in the membrane of polymersome with

The χij parameters estimated from blends module of Material Studio are also shown in the parentheses. Note that G-block is a thermosensitive polymer, and aSG varies as temperature changes. a

are not randomly selected. When species i and j are fairly compatible, one has aij ≈ 25. As the incompatibility between i and j rises, aij increases. According to Groot and Warren,24 the

Figure 2. Schematic representation of experimental declaration and snapshots of model polymer brush under various conditions. The structures of polymersomes vary with G-block length and aSG. 4781


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formed in the simulation box depends on the simulation box size. Here we show only one aggregate which displays the characteristic features of the systems. For systems capable of forming polymersomes, there are usually some micelles coexisting in the solutions. 2. Effect of Temperature on the Self-Assembly of PGMAgraf t-(PEO/PS-b-PNIPAM) Brushes. PNIPAM exhibits a lower critical solution temperature (LCST) and a remarkable coil-toglobule transition in aqueous solutions in response to changes in temperature.27 The LCST of PNIPAM homopolymer lies closely to body temperature (around 32 °C). As a consequence, temperature exerted a significant effect on the morphology of the structures of the asymmetric macromolecular brush (PGMA-graf t-(PEO/PS-b-PNIPAM)). At a temperature above LCST of PNIPAM (40 °C), thin dark rings around vesicles can be observed by transmission electron microscopy images of self-assembly aggregates. According to dynamic light scattering, the size of the vesicles decreased, and it was attributed to the shrinking of PNIPAM blocks in the corona. Since the influence of temperature on PNIPAM is manifested through the solvent quality, it can be reflected by the interaction parameter between solvent and G-block in DPD simulations. That is, the value of aSG rises with increasing temperature. Note that, in principle, all the interaction parameters between solvent and polymer (PS, PEO, PNIPAM) should change with temperature. However, as we know, the coil-to-globule transition curve of PNIPAM hydrogel is quite sharp, indicating a rather significant change in the interaction parameter of water−PNIPAM (aSG) around 32 °C. On the other hand, from the analyses of Materials Studio’s polymer and simulation modeling software, there are only slight changes in the interaction parameters of water−PS and water−PEO from T = 20 to 40 °C. As a consequence, for simplicity, only aSG (water−PNIPAM) was varied to study the effect of temperature on the vesicular morphology. Our simulations of the model polymer brushes confirms the experimental findings and show that the resulting polymersome decreases in size quite sharply as temperature exceeds the LCST, as illustrated in Figure 3a. Also, it is clear that the membrane thickness grows abruptly at LCST. A roughly 2-fold increase is found. This result indicates that for temperature greater than LCST there should be a significant conformation change other than the shrinking of PNIPAM blocks in the corona. Detailed examinations of the polymersome structures reveal that polymersomes transform from an asymmetric fourlayered conformation to a symmetric seven-layered configuration, as illustrated in Figure 3b. For temperature below PNIPAM’s LCST, PNIPAM is soluble in water. Both PEO and PNIPAM blocks can form the corona of the polymersome, and therefore a membrane with a sequence of PNIPAM-PS-PGMAPEO (G-B-Y-R) resulted. However, PNIPAM becomes insoluble once temperature is above the LCST. The PEO block is now the only soluble block in the system and forms both the inner and outer coronas of the polymersomes. Because of the specific architecture of the polymer brush and interaction energy consideration, the PNIPAM blocks can only exist as the middle layer of the hydrophobic shell leading to a membrane with a sequence of PEO-PGMA-PS-PNIPAM-PS-PGMA-PEO (R-Y-B-G-B-Y-R). In this regard, the membrane thickness should increase roughly 2 times as PNIPAM’s LCST is exceeded. Indeed, it is found that the membrane thickness of the symmetric seven-layered polymersome is roughly twice as larger as that of the asymmetric four-layered one.

temperature are also monitored. Second, the morphological phase diagram of Y15-graf t-(Rx/By-b-Gz) at polymer concentration φp = 0.05 is displayed to demonstrate the effects of Band G-block lengths. The representative morphological snapshots are also shown. Third, the effect of molecular architecture is also illustrated by morphological snapshots and crosssectional slices. Finally, the effects of grafting density on the self-assembled behaviors are examined. A. Comparisons between Experiments and Simulations. 1. Self-Assembly of PGMA-graf t-(PEO/PS-b-PNIPAM) Brushes in a Selective Solvent. Because of the unique amphiphilic asymmetric structure of PGMA-graf t-(PEO/PS-bPNIPAM), the polymer brush tends to self-assemble into polymersomes within selective solvents.11 Lian et al. suggested that the polymersome has an asymmetric multilayered conformation as illustrated in Figure 2a. The long solvophilic PNIPAMs stay on the outermost rim of the polymersome while the short solvophilic PEO side chains exist on the innermost rim of the polymersome. The solvophobic PGMA backbone and PS blocks form the inner and outer shells of the membrane. Such a polymersome scenario can be examined by DPD simulations. In our study, the asymmetric macromolecular brushes PGMA-graf t-(PEO/PS-b-PNIPAM) is modeled by the polymer brush Y15-graf t-(Rx/By-b-Gz) as shown in Figure 1. The solvophobic PGMA backbone is represented by Y15, the yellow-colored block. The solvphilic PEO side chain is labeled as Rx, the red-colored block. The PS-b-PNIPAM side chain is designated as By-b-Gz, the blue-colored and the green-colored diblock. Our simulation results of Y15-graf t-(R1/B7-b-G2) in selective solvents confirm that an asymmetric four-layered polymersome can be spontaneously formed within the solution. The internal structures of the polymersomes as illustrated in Figure 2b agree with the experimental declaration. This outcome validates our proposed polymer brush model and interaction parameters, which allow us to explore the behavior of those systems further. When a slight modification of the polymer brush is made by decreasing the G-block length (from G2 to G1), a significant structural change in the polymersome is resulted. The solvophilic G-blocks are found to stay preferentially on the innermost rim of the polymersome, and the R-blocks form the outermost layer as in Figure 2c. In addition, since the R-blocks are directly attached to the solvophobic backbone (Y-blocks), the Y-layer moves outward accordingly. As a consequence, an inverted asymmetric four-layered polymersome develops, and it has a membrane consisting layers in the outward order of G-BY-R, which are in opposite sequence as those of Figure 2b. That is, when the length of PNIPAMs becomes shorter, the solvophilic layer formed by PNIPAMs changes from the innermost rim to the outmost border. This result reveals that the variation of the solvophilic block length or the solvophilic strength can affect the final conformation. In an attempt to verify this conjecture, we increase the solvophilicity of the Gblock, that is, aSG is tuned down from 15 to 10 while keeping the G-block length to be 1. G-blocks are observed to move from the innermost rim to the outermost border, i.e., in the order of R-Y-B-G as shown in Figure 2d. The above outcome indicates that the structural arrangements of the polymersomes are the result of competition between the entropic and enthalpic effects of the two solvophilic blocks. The morphological structure of the polymersome can be systematically manipulated by adjusting the block length or the strength of the solvophilic interaction. Note that the number of aggregates 4782


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to stabilize the structure.11 In addition, it was found that the average size of the structure increased with PS chain length. A model polymer brush, Y15-graf t-(R1/By), was constructed accordingly in our work, where Y, R, and B correspond to PGMA, PEO, and PS respectively. The B-block length is varied from 3 to 13. Note that according to the analyses of Materials Studio’s polymer and simulation modeling software, the interaction parameters for water−polymer and methanol− polymer are quite comparable, except that PS is slightly more soluble in methanol than in water. The self-assembly of PGMAgraf t-(PEO/PS) brushes in methanol should be qualitatively similar to that in water. Therefore, the interaction parameters listed in Table 1 are also applied here. Our simulation results also show that these brushes can spontaneously form polymersomes in selective solvents. The averaged size of the polymersome grows as y increases as shown in Figure 4. The

Figure 4. Vesicular radius of the polymersome formed by model polymer brush (Y15-graft-(R1/By)) with various y. Here, the number concentration of polymer brush is fixed.

simulation result is consistent with the experimental findings.11 In addition, we found that the outer radius grows more significantly than the inner radius, and this result denotes that the membrane thickness increases with B-block length. Detailed inspection of the internal structure of the polymersome reveals that the polymersome has a symmetric five-layered membrane. As expected, being the only soluble blocks, the R-blocks extend from the inner and outer surfaces into the solvent to shield the solvophobic blocks. Again, since the R-blocks are directly attached to the solvophobic backbone (Y-blocks), the Y-blocks are distributed into two shells enclosing B-blocks. A membrane with a sequence of R-Y-B-Y-R resulted, as illustrated in Figure 4. B. Morphological Phase Diagram of Y15-graf t-(R1/Byb-Gz). As we have illustrated in the previous section, the relative length of the amphiphilic diblock side chain (B-b-G) of the polymer brushes has a significant impact on the overall morphologies and internal structures of self-assembly. Aggregates with various conformations can be developed. In this

Figure 3. (a) Variation of the polymersome size and membrane thickness with the interaction parameter aSG (temperature). LCST of G-block is indicated by the arrow. (b) Structure comparison between the membranes of polymersomes at temperatures higher than LCST and lower than LCST.

3. Self-Assembly of PGMA-graf t-(PEO/PS) Brushes. Lian et al. also synthesized another asymmetric macromolecular brush with PEO and PS side chains (PGMA-graf t-(PEO/PS)).11 These brushes can also self-assemble into vesicle structures in methanol, a solvent for PEO and a precipitant for PGMA backbone and PS side chains. Note that PEO is the only soluble block in this macromolecular brush which is different from the aforementioned PGMA-graf t-(PEO/PS-b-PNIPAM) brush. The experimental results inferred that the collapsed PS side chains constitute the center of the membrane to avoid unfavorable interaction with methanol, while the soluble PEO chains extend from the inner and outer surfaces into methanol 4783


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Figure 5. (a) Morphological phase diagram of aggregates formed by polymer brush Y15-graft-(R1/By-b-Gz). (b) Characteristic morphological snapshots are illustrated for various B-block lengths (y) and G-block lengths (z).

symmetric five-layered vesicle (type A polymersome), inverted asymmetric four-layered vesicle (type B polymersome), and asymmetric four-layered vesicle (type C polymersome). In general, vesicles take shape for long enough B-block length and micellar-like aggregates develop for short B-block length. The characteristic morphological snapshots are illustrated in Figure 5b. As the length of the solvophobic B-block is short (lower part of the phase diagram shown in Figure 5b), polymer vesicles cannot be formed. The morphological structures of these aggregates are significantly affected by the length of solvophilic G-block. For longer G-block, each polymer brush are able to form a spherical micelle itself. That is, polymer brushes are dispersed in the solution and become unimolecular micelles which are similar to typical micelles with the solvophobic core shielded by G-blocks. As the G-block

section, we intend to investigate the effects of lengths of Bblock and G-block on the self-assembled behaviors of polymer brushes by constructing the morphological phase diagram. Without loss of generality, we fix the solvophilic block as R1 and backbone as Y15 for our model polymer brush Y15-graf t-(R1/Byb-Gz). The B-block length varies from 1 to 9, and G-block length changes from 0 to 5. Note that the increase in B-block length indicates the growth in the solvophobic strength of the polymer brush. On the contrary, the increase in the G-block length enhances the solvophilicity of the polymer brush. In this section, the polymer concentration is set as φp = 0.05. Figure 5a is the morphological phase diagram of Y15-graf t(R1/By-b-Gz) as a function of the B-block length (y) and the Gblock length (z). Six distinct types of aggregates are observed: porous aggregate, worm-like micelle, unimolecular micelle, 4784


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Figure 6. Effects of the solvophilic side chain (R-block) on the morphology of the self-assembly formed by asymmetric polymer brushes Y15-graft(Rx/B7-b-G2) and Y15-graf t-(Rx/B7).

copolymers28 and Kong et al. on ABC star copolymers29 all showed a variety of aggregative morphologies, such as vesicles, laterally structured vesicles, hamburger micelles, segmented bilayer sheets, multicompartment worms, and onions. Clearly, these simulation results demonstrate that the membrane structure of the polymersome varies significantly with the block copolymer architecture. In addition, the morphological diagrams of aggregates also change significantly with the molecular architectures. C. Effect of Solvophilic Side Chain (R-Block). The Rblock of our model polymer brush Y15-graf t-(Rx/By-b-Gz) corresponds to the PEO block in the asymmetric polymer brush PGMA-graft-(PEO/PS-b-PNIPAM). Unlike solvophilic G-blocks, the solvophilic R-block is directly connected to the backbone Y-block. As a result, it plays a nontrivial role in determining the morphological conformation of the selfassembly formed by polymer brushes. As we have mentioned in the previous sections, asymmetric four-layered polymersome can be spontaneously formed by model polymer brush Y15graf t-(R1/B7-b-G2) as shown in Figure 6b. However, there exists a delicate balance between the lengths of the two solvophilic blocks. As the length of R-block is increased, the aggregate becomes a sheet-like micelle as illustrated in Figure 6c, and this multicompartment micelle has a unique asymmetric layout with R-blocks shielding Y-blocks and G-blocks protecting B-blocks. Further increase in the R-block length, each polymer brush develops a unimolecular micelle as demonstrated in Figure 6d. The unimolecular micelle is formed because the solvophilicity of the brush grows with the R-block length. In fact, R-blocks become the major part of the corona shielding the unfavorable solvophobic interactions between solvents and Y/B-blocks. Note that since R-blocks are directly connected to the Y-blocks, Y-blocks can only exist on the outer

becomes shorter, worm-like micelles are developed due to geometrical packing. For even shorter G-blocks, worm-like micelles entangle with each other to form porous aggregates. The other solvophilic side chain (R-block) becomes the main shield against solvophobic contacts. Generally, as G-block length increases, the aggregates transform from porous, wormlike to spherical unimolecular micelles. The sizes of the aggregates decrease accordingly because the solvophilicity of the polymer brush grows with G-block length. The polymersomes exist in the upper part (long B-block length) of the phase diagram (Figure 5). However, the internal conformations of the polymersome are greatly affected by the G-block length. The polymersomes transform from type A, type B to type C polymersome as G-block length increases. In the absence of G-block, type A polymersome is formed, and it has a symmetric five-layered membrane with an outward order, R-Y-B-Y-R. When G-block is short, type B polymersome develops. Type B polymersome has an inverted asymmetric four-layered (G-B-Y-R) structure. When G-blocks are long, they prefer to stay at the outer surface of the membrane, instead of the inner surface for type B polymersomes, so that the steric repulsion between extended G-blocks in the solvent can be reduced. As a consequence, a polymer vesicle with an asymmetric four-layered (R-Y-B-G) structure takes shape. Evidently, the membrane characteristics associated with various types of polymersomes are different and can be controlled by the B-block and G-block lengths. In this work, the polymer brush consists of a solvophobic backbone attached with two different side chains: solvophilic and amphiphilic diblock. This molecular architecture is quite unique, and specific self-assembled morphologies such as asymmetric four-layered polymersomes are formed. The works of Cui and Jiang on linear ABCA tetrablock 4785


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Figure 7. Effects of molecular architecture on the morphology of the self-assembly formed by asymmetric polymer brushes with a fixed composition (Y15/R1/B7/G2).

self-assembled aggregates. That is, at a fixed composition of polymer brushes (Y15/R1/B7/G2), the morphology of the selfassembly depends on the structural arrangement of the two solvophilic blocks, R1 and G2, in the molecule. Figure 7 shows the effect of molecular architecture with six types of arrangements on the aggregate morphology. As shown in Figure 7a−c, asymmetric polymersomes are formed when the two solvophilic blocks are separately attached to the backbone and the side chain, i.e., (a) two side chains grafted to the same backbone unit with R1-Y15 and G2-B7-Y15, (b) two side chains grafted alternatively with R1-Y15 and G2-B7-Y15, and (c) two side chains grafted to the same backbone unit but with G2-Y15 and R1-B7-Y15. Polymersome of Figure 7c has a membrane with different layer sequence, R-B-Y-G, as compared to the polymersomes of Figure 7a,b with R-Y-B-G. This is because G-blocks tend to stay as the outer protective layer due to the entropic effect and thereby force the backbone Y-blocks, which are connected to the G-blocks, to move to outer shell. In addition, their vesicle sizes are evidently different, and this fact reveals that their membrane properties may be quite distinct. On the other hand, only micellar aggregates are observed when both the solvophilic blocks are attached to the solvophobic backbone or the solvophobic side chain as demonstrated in Figure 7d−f, i.e., (d) R1 and G2 grafted to the backbone alternatively, (e) G2-b-R1 side-chain grafted to the backbone, and (f) R1-b-G2 connected to B7-Y15 to form a side chain. Different from typical micelles, these micellar aggregates have multiple domains, which are essentially organized in a core−shell−corona manner. It is worth mentioning that these multicompartment micelles are all small sized as compared to the polymersomes. This findings indicates that the polymer brush are more solvophilic when the two solvophilic blocks are closely located. It may be explained by geometric packing considerations. The resulting morphologies also show that as

rim of the solvophobic core in spite of the fact that they are the most solvophobic block of the polymer brush. For a polymer brush not possessing any R-block, a hamburger-like micelle with core−shell−corona conformation is observed as shown in Figure 6a. This outcome is as expected since the G-block is the only solvophilic block of the polymer brush. As demonstrated in experiments and simulations for polymer brush not possessing any G-block, i.e., Y15-graf t-(Rx/B7), a symmetric five-layered polymersome can be formed spontaneously in selective solvents (Figure 6f). When the R-block increases in length, the aggregate no longer takes the form of a vesicle. Instead, a mooncake-like micelle with core−shell− corona conformation develops, as illustrated in Figure 6g. The core is formed by B-blocks while the shell consists of Y-blocks. As the R-block length is further increased, the micelle becomes spherical and smaller in size as shown in Figure 6h. Note that for a polymer brush without both G- and R-blocks, there are only solvophobic blocks in the system. The incompatibility between the polymer brush and the solvent leads to phase separation within the system. The above results clearly point out the significant effect of the R-block on the morphological outcomes of the self-assembled aggregates by our model polymer brushes. In general, as the R-block length (x) declines, the aggregate formed by Y15-graf t-(Rx/B7) varies from core− shell−corona micelles to vesicles and the aggregate size is increased as well. D. Effect of Molecular Architecture. It is known that the micellar behavior of block copolymers depends significantly on molecular architecture.30 As we have shown in the previous sections, a unique asymmetric multilayered polymersome develops for the asymmetric polymer brush and the asymmetric feature is resulted from the existence of two solvophilic blocks within the molecule. The location of the solvophilic block seems to significantly affect the resulting morphologies of the 4786


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Figure 8. Effects of grafting density on the morphology of the self-assembly formed by asymmetric polymer brushes Y15-graf t-(R1/B7-b-G2).

block center, B-block shell, and G-block corona. Note that the corona covers the top and bottom of the hamburger, but the solvophilic R-blocks are not part of the corona to shield the unfavorable interactions between solvophobic blocks and solvents. Instead, they are situated within the center and intermixed with the Y-blocks. However, R-blocks do surround the edge of the hamburger. This can be explained by the fact that it is insufficient to sequester the backbone Y-block from solvent by the R-block as the grafting density is low. Since the solvophobic interactions between Y-blocks and solvents are the strongest, it is imperative to hinder the Y-block/solvent contacts. As a consequence, the interfacial energy is lowered when Y-blocks become the center protected by the B- and Gblocks. Because the R-blocks are directly attached to the Yblocks, R-blocks become part of the micellar core in spite of their solvophilic characteristics. Nonetheless, R-blocks protect the edge of the Y-block center partially from the solvent. In summary, the increment of the grafting density leads to the change of the aggregate morphology from hamburger-like micelles, vesicles, to donut-like micelles.

the solvophilic blocks are attached to the backbone Y-blocks, the micelles have B-blocks as the inner core and Y-blocks as the outer shell of the micelles (Figure 7d,e). Otherwise, the Yblocks which are the most solvophobic block form the inner core, which is then protected by the B-blocks shell and solvophilic R/G-blocks corona (Figure 7f). E. Effect of Grafting Density. In addition to the effects of solvophilic block length and molecular architecture, the grafting density influences backbone rigidity and solvophobicity and is also an important factor that affects the self-assembled morphological conformation of polymer brushes in selective solvents. As shown in Figure 8, aggregates of distinct morphologies are resulted from polymer brushes of various grafting density for Y15-graf t-(R1/B7-b-G2). Three cases, which are distinguished by the distance between side chains, are considered: high (one bead), moderate (two), and low (three) grafting densities. At moderate grafting density which has been studied in previous sections, asymmetric four-layered vesicle is observed as shown in Figure 8b. At high grafting density, however, unique worm-like or donut-like aggregate develops for polymer brushes at concentration φp = 0.03, as illustrated in Figure 8a. The increase in grafting density leads to the increase in the solvophobicity of the polymer brush because solvophobic B-blocks become more and more dominant. These polymer brushes self-assemble into worm-like micelles. For long enough worm-like micelle, donut-like micelle forms in order to reduce edge effect associated with both ends. At low grafting density, symmetric multicompartment micelles develop as depicted in Figure 8c. A hamburger-like micelle with the multilayer structure, which can also be formed by miktoarm star ABC terpolymer,31 is identified with the Y/R-

IV. CONCLUSION The self-assembly behavior of amphiphilic asymmetric macromolecular brushes Y15-graf t-(Rx/By-b-Gz) which is a representative of PGMA-graft-(PEO/PS-b-PNIPAM) in a selective solvent is explored by DPD simulations, which can offer valuable microscopic insights and complement the deficiency of experimental studies on the aggregation. The macromolecular brush consists of a solvophobic backbone Y-block, solvophilic side chains (R-block), and diblock side chains made of solvophobic B-block and solvophilic G-block. The aggregate 4787


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like micelles with the symmetric multicompartment structure develop at low grafting density.

of these polymer brushes exhibits a rich variety of morphological conformations. Dependent on the block length associated with R-, B-, and G-blocks (x, y, and z), molecular architecture, and grafting density, the morphology of the selfassembly includes five types of multilayered vesicles: porous aggregates, worm-like micelles, donut micelles, hamburger micelles, and unimolecular micelles. In order to confirm the validity of our DPD model of asymmetric polymer brush, we compare our simulation findings with the experimental results by Lian et al. An asymmetric fourlayered polymersome in the outward order of R-Y-B-G is spontaneously formed by polymer brushes Y15-graf t-(R1/B7-bG2). This result is in agreement with the experimental observation. Since PNIPAM (G-block) exhibits LCST in aqueous solutions around 32 °C, temperature has a significant influence on the morphology of the polymersome structure. Based on the change of solvent quality for G-block, our simulation of the model polymer brushes show that the resulting polymersome decreases in size quite sharply as temperature exceeds the LCST. This finding is also consistent with the experimental observation. When PNIPAM is absent, i.e. z = 0, a symmetric five-layered polymersome (R-Y-B-Y-R) is formed by Y15-graf t-(R1/By). It is found that the vesicle size grows with increasing the B-block length (y). Again, the simulation and experiment agree with each other. The influences of the block length on the morphological conformations of the self-assembly formed by our model polymer brushes is then investigated. The morphological phase diagram of Y15-graft-(R1/By-b-Gz) is obtained as a function of the B-block length (y) and the G-block length (z). Six distinct types of aggregates are observed: porous aggregate, worm-like micelle, unimolecular micelle, symmetric five-layered vesicle (type A polymersome), inverted asymmetric four-layered vesicle (type B polymersome), and asymmetric four-layered vesicle (type C polymersome). In general, vesicles are formed for long enough B-block length and micellar-like aggregates develop for short B-block length. In general, the sizes of the aggregates decrease with increasing G-block length because the solvophilicity of the polymer brush grows accordingly. The effect of solvophilic side-chain length (x) is demonstrated by considering polymer brush Y15-graf t-(Rx/B7-b-G2). As the length of R-block is increased, the aggregate morphology changes from hamburger micelle, vesicle, asymmetric sheet, to unimolecular micelle. They are the consequence of the delicate balance between the lengths of the two solvophilic blocks. In addition to the effect of block length, molecular architecture and grafting density are also important factors that influence the self-assembled morphological conformation of polymer brushes in selective solvents. At a fixed composition of polymer brushes (Y15/R1/B7/G2), the morphology of the self-assembly varies with the structural arrangement of the two solvophilic blocks, R1 and G2, in the macromolecule. Asymmetric polymersomes are formed when the two solvophilic blocks are separately attached to the backbone and the side chain. On the other hand, only micellar aggregates are observed when both the solvophilic blocks are attached to the solvophobic backbone or the solvophobic side chain. For Y15-graf t-(R1/B7-b-G2), aggregates of distinct morphologies are resulted from polymer brushes of various grafting densities, which are characterized by the distance between side chains. Although asymmetric four-layered vesicle is observed at moderate grafting density, unique worm-like or donut-like aggregates are formed for high grafting density, but hamburger-

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (Y.-J.S.); [email protected] (H.-K.T.). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This research work is supported by National Science Council of Taiwan. Computing times, provided by the National Taiwan University Computer and Information Networking Center and National Center for High-performance Computing (NCHC), are gratefully acknowledged.

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REFERENCES

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Multilayered Polymersome Formed by Amphiphilic Asymmetric

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