POLYMERS

Simultaneous covalentand noncovalenthybrid polymerizationsZhilin Yu,1 Faifan Tantakitti,2 Tao Yu,1 Liam C. Palmer,1,3

George C. Schatz,1,4 Samuel I. Stupp1,2,3,5,6*

Covalent and supramolecular polymers are two distinct forms of soft matter, composedof long chains of covalently and noncovalently linked structural units, respectively.We report a hybrid system formed by simultaneous covalent and supramolecularpolymerizations of monomers. The process yields cylindrical fibers of uniform diameterthat contain covalent and supramolecular compartments, a morphology not observedwhen the two polymers are formed independently. The covalent polymer has a rigidaromatic imine backbone with helicoidal conformation, and its alkylated peptide sidechains are structurally identical to the monomer molecules of supramolecular polymers.In the hybrid system, covalent chains grow to higher average molar mass relative tochains formed via the same polymerization in the absence of a supramolecularcompartment. The supramolecular compartments can be reversibly removed andre-formed to reconstitute the hybrid structure, suggesting soft materials with noveldelivery or repair functions.

Supramolecular soft matter encompassesorganic materials in which structural unitsengage in strong and often complex non-covalent interactions to generate specificproperties and functions. Structurally,

these materials can be organized nanostruc-tures (1) or supramolecular polymers (2). Supra-molecular soft matter has obvious potentialto create reversibly dynamic materials, giventhe finite lifetimes of interunit noncovalentbonds, and development of this area is clearlyinspired by biological systems. In cytoskeletonfibers, for example, the monomers are covalentpolymers, and it is their reversible noncova-lent interactions into a supramolecular poly-mer that create their dynamic functions incells (3, 4). Variations in monomer structures(5, 6), covalent templates (7), or catalysts (8)have facilitated great progress toward the de-sign of supramolecular architectures in solution.However, the integration of covalent and su-pramolecular polymers into hybrid dynamicstructures as a source of function has yet to beachieved.

Here we report the synthesis of polymericsystems based on the simultaneous covalentand noncovalent polymerization of structurallymatched monomers. We aimed to explore thenature of hybrid structures that might form dur-ing this potentially synergistic process. The co-valent polymer (C-Polymer) was designed to form

by condensation reactions between an aromaticdialdehyde (monomer 1) and an aromatic di-amine (monomer 2). These two monomers con-tained as side chains the amino acid sequencevaline–glutamic acid–valine–glutamic acid, con-nected to the aromatic groups via a dodecyl link-age (Table 1). Monomer 3 of the supramolecularpolymer (S-Polymer) (Table 1) is isostructuralwith the side chains of the C-Polymer and, on thebasis of previous results, was expected to formribbon-shaped supramolecular polymers (9).Consistent with previous work on foldamers(10–12), the C-Polymer was designed to have asixfold helicoidal conformation, in this case pro-moted in polarmedia and stabilized by hydrogenbonds among the peptide segments, as well as p-pstacking interactions between aromatic groups.To synthesize the C-Polymer, we mixed mono-

mers 1 and 2 in a 1:1 molar ratio in aqueoussolution at pH 5 to promote the condensationreaction between aldehydes and amines (13).The S-Polymer formed by simply dissolving mono-mer 3 in water, owing to its strong amphiphilicstructure. Cryo–transmission electron micros-copy (cryo-TEM) revealed the formation of aheterogeneous collection of one-dimensional(1D) structures in the C-Polymer (Fig. 1A andfig. S9), and the S-Polymer formed the expectedribbon-shaped flat assemblies (Fig. 1B). How-ever, when we mixed solutions of monomers 1, 2,and 3 simultaneously in a molar ratio of 1:1:2at pH 5, the flat assemblies of the S-Polymerdid not form, and we instead observed 1D struc-tures with precisely defined cylindrical shapewith uniform diameter as the dominant morphol-ogy (in a few uncommon sites, thin ribbonlike

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1Department of Chemistry, Northwestern University, 2220Campus Drive, Evanston, IL 60208, USA. 2Department ofMaterials and Science and Engineering, NorthwesternUniversity, 2220 Campus Drive, Evanston, IL 60208, USA.3Simpson Querrey Institute for BioNanotechnology,Northwestern University, 303 East Superior Street, 11th floor,Chicago, IL 60611, USA. 4Department of Chemical andBiological Engineering, Northwestern University, 2220Campus Drive, Evanston, IL 60208, USA. 5Department ofMedicine, Northwestern University, 2220 Campus Drive,Evanston, IL 60208, USA. 6Department of BiomedicalEngineering, Northwestern University, 2220 Campus Drive,Evanston, IL 60208, USA.*Corresponding author. E-mail: s-stupp@northwestern.edu

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defects can be observed) (Fig. 1C and fig. S10).These 1D structures appear well separated,which is possibly the result of the high chargedensity contributed by the integration of theS-Polymer in the hybrid structure.

We hypothesized that a covalent-noncovalent(CNC) hybrid system was formed by the simul-taneous covalent and supramolecular polymer-izations. More specifically, we considered thatthis CNC hybrid integrated distinct covalent

and supramolecular compartments as a re-sult of the structural match of their respectivemonomers (Fig. 1, D to H). In addition, weobserved only a homogeneous cylindrical struc-ture, suggesting thorough integration of both

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Fig. 1. Hybrid CNC polymers. (A to C) Cryo-TEM images for (A) thecovalent polymer (C-Polymer) obtained bymixing monomers 1 and 2 in a 1:1molar ratio at pH 5 (white arrows point to ribbonlike segments and blackarrows to cylindrical ones), (B) the supramolecular polymer (S-Polymer)formed by monomer 3, and (C) the CNC hybrid polymer obtained by simul-taneously mixing monomers 1, 2, and 3 in a molar ratio of 1:1:2 at pH 5.(D to G) Molecular graphics illustrations of (D) the covalent polymerization

of monomers 1 and 2 [including a magnified representation (E)], (F) thesupramolecular polymerization of monomer 3, and (G) the simultaneouscovalent and supramolecular polymerizations that yield the hybrid polymer.Phenyl moieties in molecular graphics illustrations in (D), (E), and (G) areshown in yellow. (H) Schematic representation of the CNC hybrid polymerconsisting of two distinct covalent (green and yellow) and supramolecular(red) compartments.

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polymers. Mechanistically, the preference forhelical conformation in the C-Polymer and com-mon structural features in all three monomerscould guide directional nucleation and growthof supramolecular compartments to create acylindrical hybrid structure.The morphologies of the C-Polymer and the

CNC hybrid were also investigated using atomicforce microscopy (AFM). In the hybrid samples,AFM experiments revealed the uniform, well-separated fibrils observed with cryo-TEM (fig.S12C), whereas the mixture of monomers 1 and2 formed bundled fibrous structures (fig. S12B).We attribute the bundling (which was not ob-served with cryo-TEM) to drying effects as wateris removed. This bundlingwas not observedwithAFM when all three monomers (1, 2, and 3)

were mixed simultaneously, providing furtherevidence of the integration of monomer 3 in thehybrid, which should result in highly chargedsurfaces.We first used optical spectroscopy to in-

vestigate the condensation between monomers1 and 2 to form the C-Polymer. A 1:1 molarratio of monomers 1 and 2 in a fresh solutionat pH 5, which favors formation of imine bondsfor polymerization, yielded a product revealingin its fluorescence spectrum the anticipatedexcimer emission appearing instantaneouslyat 430 nm, compared with 358 nm for mono-mer 1 (Fig. 2A). This shift indicates the ex-istence of strong p-p stacking interactions inthe folded backbone of the C-Polymer (14).Immediately upon mixing monomers 1, 2,

and 3, we observed substantial quenching ofthe excimer emission characteristic of the C-Polymer, which is expected with lengtheningof the folded backbone (14). This observationand the absence of monomer emission at358 nm suggest that the covalent polymeri-zation of monomers 1 and 2 within the hybridwas facilitated by the simultaneous polymeri-zations (Fig. 2A).The typical circular dichroism (CD) signals

for b-sheet secondary structure in the peptideside chains were observed in the mixture ofmonomers 1 and 2 (Fig. 2B), whereas onlyCD signals corresponding to random coil con-formation were observed for the individualmonomers (fig. S6). These results indicatethat attachment of the peptide to the C-Polymer

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Fig. 2. Spectroscopic characterization. (A) Fluorescence spectra of monomer 1, the C-Polymer, and the hybrid CNC polymer. Fluorescence ismeasured in units of counts. l, wavelength. (B) CD spectra of the C-Polymer, the S-Polymer, the hybrid CNC polymer, and the sum of the spectra of theC-Polymer and S-Polymer. (C) Plot of the difference in CD signal intensity at 214 nm, corresponding to the mixture of all three monomers (1, 2, and 3) andthat of monomer 3 [Dellipticity = CD intensity (mixture) – CD intensity (monomer 3)], as a function of the added equivalents of monomer 3. All sampleswere prepared at pH 5.

Fig. 3. Extraction and reconstitution. (A to C) Cryo-TEM image of (A) the CNC hybrid polymer, (B) the same material after extraction of the supramolecularcompartments by dialysis, and (C) after reconstitution of the hybrid by adding a fresh solution of monomer 3. (D and E) Images corresponding to samplesexposed to a second cycle of extraction and reconstitution. (F) Schematic representation of the extraction of supramolecular compartments from CNC hybridpolymers and their reconstitution by adding monomer 3.

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backbone as a side chain enhanced formationof the b sheets. In turn, these hydrogen bondscan facilitate the growth of the folded backboneby preorganizing monomers. In addition, theabsence of a CD signal in the absorption re-gion of the folded backbone (~300 nm) indi-cates that the chiral centers in peptide segmentsare too distant or the dodecyl linkers are tooflexible to bias the twist sense of the helicalbackbone (15). When solutions of monomers1, 2, and 3 were mixed simultaneously, theCD signal for b sheets increased relative tothat of the C- or S-Polymer, and the signal in-tensity was even greater than the sum of both(Fig. 2B). This increase suggests the forma-tion of a highly integrated hybrid structure inwhich peptide hydrogen bonding is enhancedthrough synergistic interactions among thethree isostructural monomers. The increase inCD intensity depended on the relative concen-trations of monomers 1 and 2 versus monomer3, and the saturation of the signal was ob-served beyond the addition of two equivalentsof monomer 3 (Fig. 2C). We also used cryo-TEMto examine samples resulting from mixturesof monomers 1, 2, and 3 with molar ratios of1:1:1 and 1:1:4. In both mixtures, we observeda heterogeneous population of structures (fig.S11). Although adding one equivalent of mono-mer 3 into monomers 1 and 2 gives rise toformation of short cylindrical fibers and rib-bons, the mixture containing four equivalentsof monomer 3 forms long fibers and ribbons.These results indicate that there is not enoughmonomer 3 in the first case to form the high-ly defined structure of the CNC hybrid. How-ever, an excess of monomer 3 in the secondcase leads to the formation of the CNC hybridand a ribbon-shaped S-Polymer. On the basisof CD data and cryo-TEM images, we concludethat the supramolecular compartments areformed only by a finite number of monomer3 molecules per unit length of hybrid struc-ture (Fig. 1G). This is consistent with the well-defined shape and largely uniform diameter ofhybrid fibrils.We tested the possibility of removing the

supramolecular compartment from the hybridCNC polymer and subsequently reconstitutingit. We synthesized a fluorescein-labeled versionof monomer 3 (fl-3) to quantify this process.Cryo-TEM experiments showed that extractionof monomer 3 from the hybrid by dilution inpH 5 water and dialysis led to the appearanceof short fibers (Fig. 3B). Upon addition of freshmonomer 3 to the extracted sample, the longcylindrical morphology of the CNC hybrid wasrecovered (Fig. 3, A to C), and when the extrac-tion and reconstitution cycle was repeated,identical results were obtained (Fig. 3, D and E).Based on the fluorescence intensity of fl-3 inthe polymer solution, 94% of monomer 3 wasremoved from the hybrid after dilution anddialysis (fig. S17).To verify covalent polymerization in both the

C-Polymer and the CNC hybrid, we used Fouriertransform infrared (FTIR) spectroscopy, matrix-

assisted laser desorption/ionization–time-of-flight (MALDI-TOF) mass spectrometry, andsize exclusion chromatography with multianglelight scattering (SEC-MALS). The FTIR mea-surements provided evidence of imine bondformation in both the C-Polymer and the CNChybrid (fig. S3), as well as the presence of hy-drogen bonds in all samples (fig. S3). MALDI-TOF studies also confirmed the formation ofcovalent polymer upon mixing monomers 1 and2 or monomers 1, 2, and 3, as indicated by anappropriate increase in molar mass in bothcases (fig. S4). The average molecular weightwhen 1 and 2 were mixed was determined bySEC-MALS to be on the order of 14 kDa, but amuch higher molecular weight of 250 kDa wasmeasured by this technique for the covalentcomponent of the CNC hybrid (fig. S5 and tableS1). Based on the average molecular weightmeasured for the covalent polymer componentof the hybrid and the cryo-TEM images, weconclude that cylindrical fibers contain mul-tiple chains condensed by the synergistic sec-ondary interactions among the three structuralunits. Overall, these results demonstrate the for-mation of a covalent polymer by mixing mono-mers 1 and 2 or within the hybrid structure.Furthermore, the results also strongly supportthe notion that formation of the supramolecularcompartment in the hybrid effectively catalyzescovalent polymerization.We analyzed the covalent component in the

CNChybrid after extraction of the supramolecularcompartment using fluorescence and SEC-MALSexperiments. Fluorescence spectra of the co-valent component after removal of the supra-molecular compartment revealed the recovery ofquenched excimer emission over time (fig. S18).This result implies that, after removal of mono-mer 3, the covalent compartment is less stableand dissociates into short covalent chains. Inaddition, the average molecular weight of thecovalent compartment aged for 10 days was de-termined by SEC-MALS to be ~16 kDa (fig. S18), adecrease of more than one order of magnituderelative to the original covalent component with-in the hybrid. Both results suggest that the CNChybrid is more thermodynamically stable thanthe C-Polymer. Furthermore, CD data as a func-tion of temperature showed that the signals forboth the C-Polymer and the CNChybrid decreasedupon heating as a result of thermally induceddepolymerization, as indicated by fluorescenceresults (fig. S7). However, in the CNC hybrid,depolymerization was found to start at a tem-perature 5°C higher than in the C-Polymer. Again,this finding provides evidence for the stabilityof the hybrid as a result of the synergistic sec-ondary interactions among its three differentstructural units. The results also provide mech-anistic insight into the CNC hybrid polymeri-zation, strongly suggesting that the synergisticinteractions are responsible for the enhancedlevels of covalent polymerization in the CNChybrid structure.We used small-angle x-ray scattering (SAXS)

experiments to further characterize the mor-

phologies of the various supramolecular assem-blies in solution. For monomers 2 and 3, thescattering signals showed a –2 slope in the low-q area (q, modulus of the momentum transfervector), demonstrating the formation of flatstructures in solution (Fig. 4A) (16, 17). The C-Polymer exhibited a –1.3 slope, which suggestsa heterogeneous mixture of morphologies, con-sistent with our cryo-TEM observations. In con-trast, the CNC hybrid displayed a slope of nearly–1 (Fig. 4A), indicating the formation of highly1D cylindrical structures without any evidenceof the flat structures observed for monomers 2and 3 (17, 18). Additional geometrical infor-mation of the assemblies of the hybrid couldbe obtained by fitting the scattering curvesto a core-shell cylinder model. The diameterfor the hybrid was estimated to be 5.9 nm,which is comparable to our observations withcryo-TEM.To gain insight into the mechanism for the

formation of the hybrid CNC polymer, we moni-tored changes in the CD spectrum over time indifferent types of samples. As shown in Fig. 4B,a mixture of monomers 1 and 2 undergoingcovalent polymerization revealed an increas-ing value of ellipticity that saturates after sev-eral hours. The CNC polymer formed by mixingall three monomers simultaneously exhibiteda rapid rise in ellipticity, suggesting nuclea-tion and growth of an ordered structure. At thesame time, the invariant ellipticity of the S-Polymer formed by monomer 3 indicates thatthe increase in ellipticity of the CNC hybrid didnot arise from independent supramolecularpolymerization, but rather from the simulta-neous supramolecular and covalent polymeri-zations. The faster kinetics associated with CNChybrid formation compared with that of theC-Polymer strongly supports a distinctive mech-anism involving simultaneous covalent andsupramolecular reactions. These observationscould explain why the average molecular weightmeasured for the covalent compartment of theCNC polymer is so much higher than that of theC-Polymer. In other words, the data are consist-ent with a synergistic enhancement of C-Polymerformation by supramolecular contacts withmonomer 3.We used CD spectroscopy to follow the in-

teraction between a pre-formed C-Polymer andmonomer 3. When different amounts of mono-mer 3 were added to the pre-formed C-Polymer,we observed only a small initial increase inCD signal intensity in the b-sheet region (Fig.4C). However, when samples with an excess ofmonomer 3 aged for 2 days, the CD intensityincreased and was comparable to that observedwhen the hybrid CNC polymers formed throughthe simultaneous mixing of monomers 1, 2,and 3 (Fig. 4C). Our SEC-MALS results in-dicate that the average molecular weight ofthe covalent component in solutions contain-ing two equivalents of monomer 3 increasedwith time from 21.1 to 190 kDa (table S1). Thefact that CD signatures of the ordered hybridare not observed immediately upon mixing

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Fig. 4. Results of SAXS, cryo-TEM, and MD modeling experiments. (A)SAXS curves and their corresponding slopes in the linear region obtainedfrom solutions of monomer 2, monomer 3, the C-Polymer, and the hybridCNC polymer (scattering curves were offset for clarity). The fitting curvefor the scattering data of the CNC hybrid is shown in purple. q, modulus ofthe momentum transfer vector; I, scattered intensity; A.U., arbitrary units.(B) Change in ellipticity at 199 nm as a function of time during formation ofthe C-Polymer, S-Polymer, and CNC hybrid polymer during simultaneouscovalent and supramolecular polymerization (by mixing monomers 1, 2, and 3),as well as the CNC hybrid polymer by adding monomer 3 to a pre-formedC-Polymer. t, time in hours. (C) Plot of the difference in CD signal intensity at214 nm, corresponding to the mixture of 1 and 2 and that of monomer 3[Dellipticity = CD intensity (mixture) – CD intensity (monomer 3)], as a func-tion of the added equivalents of monomer 3. The plot shows one curvecorresponding to a fresh sample of C-Polymer mixed with 3 and another cor-

responding to an aged sample. (D and E) Cryo-TEM images of a samplecorresponding to a fresh mixture of a pre-formed C-Polymer and monomer 3(D) and a sample of the same mixture aged for 2 days (E) (both samples con-tained two equivalents of monomer 3). Black and white arrows in (D) indicatecylindrical fibers and ribbons, respectively. (F) Results from an atomistic MDmodeling of the C-Polymer (left) and the CNC hybrid polymer (right) (green,folded aromatic backbone; red, flexible dodecyl linker; blue, the turn and randomcoil; yellow, b sheet). The white dashed ellipsoids indicate formation of hydro-gen bonding between peptides in covalent and supramolecular compartments.(G and H) MM2 MD modeling (see supplementary materials) of the matchedstructures (monomers 1, 2, and 3) next to the cryo-TEM image of the systemprepared bymixing 1, 2, and 3 in amolar ratio of 1:1:2 at pH 5 (G) and, similarly,of the mismatched structures (monomers 1, 2, and 4) with the correspondingcryo-TEM image (H) (red, monomer 3; purple, monomer 4; green, side chains ofthe covalent compartment; yellow, aromatic units of the covalent compartment).

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could be explained by diffusional barriers withinthe system imposed by the pre-formed covalentpolymer.Both SAXS and cryo-TEM experiments

supported our interpretation of the CD andmolecular weight data. In SAXS experiments,the fresh mixture of pre-formed C-Polymer andmonomer 3 revealed a slope of –1.4 in thelow-q region, indicating a heterogeneous mix-ture of morphologies. In marked contrast, wemeasured a slope of approximately –1 for theaged sample, thus demonstrating the possibilityof forming the well-defined cylindrical struc-ture of the CNC hybrid by mixing monomer 3with pre-formed covalent polymer. In addition,fitting the scattering data to a core-shell cylin-drical model yields effectively the same diameterfor structures in the aged sample and samplesobtained by the simultaneous polymerizationof monomers 1, 2, and 3 (fig. S19). Further-more, cryo-TEM also reveals virtually identicalmorphologies in these two types of samples(Fig. 4, D and E).We hypothesize that the structural match

of the supramolecular monomer with the sidechains of the covalent compartment plays acritical role in the integration of the twocompartments and the catalytic effect of thesupramolecular polymerization on covalent poly-condensation. To test this hypothesis, we useda monomer (4; see supplementary materials)for the S-polymer that would not easily inter-act noncovalently with the side chains of theC-Polymer. This monomer was also a peptideamphiphile with the same general structuralfeatures as monomer 3. However, the struc-tural match in monomer 4 relative to the sidechains is lost, both in the length of the hydro-phobic region (four additional methylene groups)and its peptide sequence (a different sequenceof two amino acids present in monomer 3,valine and glutamic acid, plus two additionalglycine residues). Cryo-TEM images of the mis-matched system reveal a heterogeneous mixtureof morphologies formed by combining mono-mers 1, 2, and 4 in the molar ratio of 1:1:2 (Fig.4H and fig. S20). Additionally, in this system weobserved only a slight difference in CD inten-sity after mixing monomers 1, 2, and 4 (fig.S21). These results demonstrate that the newsupramolecular monomer does not integratewell with covalent compartments and does notform the distinct hybrid CNC polymer. The av-erage molecular weight of the covalent com-partments in the presence of monomer 4 wascharacterized by SEC-MALS to be ~18 kDa,more than an order magnitude lower than thatof the matched system (fig. S21). We concludefrom these results that the structural mismatchbetween monomer 4 and the side chains of theC-Polymer does not promote synergistic inter-actions responsible for stabilization of the C-Polymer by the S-Polymer, which in turn resultsin greater growth of the C-Polymer within theCNC hybrid.In previous work (19–22), including our own

(23–25), systems have been studied in which

covalent polymerization is triggered after supra-molecular self-assembly of monomers, leadingto internally ordered covalent polymers. Thereis also another system in which an ordered co-valent polymer was obtained after polymeriza-tion of the monomer in a solvent that does notpromote formation of a supramolecular tem-plate (26). In our current work, a pathway isdescribed to obtain hybrid polymers in whichsupramolecular and covalent polymers are inte-grated. The supramolecular compartment inthese systems can be temporarily removed andreconstituted by simply adding its monomeragain. Furthermore, we discovered that the su-pramolecular compartment within the hybridcatalyzes covalent polymerization.We carried out atomistic molecular dynam-

ics (MD) simulations on the C-Polymer andthe hybrid CNC polymer (Fig. 4F). These MDsimulations were performed for 24 moleculeseach of monomers 1 and 2 and 48 moleculesof monomer 3 in the presence of water andsodium ions. Details of these simulations canbe found in the supplementary materials andin a previous publication (27). The simulationsyielded a hybrid CNC structure with a diam-eter equal to 7 nm, which is reasonably con-sistent with experimental results (fig. S23).The simulations showed also that b sheetsformed among 15 peptide segments within theC-Polymer and 22 peptide segments in the hy-brid CNC polymer (fig. S23). Most of the bsheets within the CNC hybrids formed betweenthe supramolecular and covalent compartments(fig. S23 and MD simulations in the supplemen-tary materials). We believe that the integrationof the two distinct compartments into the CNChybrids benefits from these secondary bonds,along with other noncovalent interactions. Thisintegration among isostructural components inall three monomers was an important molecu-lar design criterion.These polymers self-organize to contain

distinct covalent and supramolecular compart-ments that allow removal and re-formation ofthe supramolecular component, thus recon-stituting the hybrid polymer. These structurescould provide functional platforms for novelmodes of molecular delivery or repair of struc-tures, as hybrids are disassembled and re-formedby simple addition of small molecules. Our ex-perimental results on these systems also sug-gest that supramolecular polymerizations canbe used to catalyze the formation of covalentmacromolecules.

REFERENCES AND NOTES

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945–951 (2009).10. D. J. Hill, M. J. Mio, R. B. Prince, T. S. Hughes,

J. S. Moore, Chem. Rev. 101, 3893–4012 (2001).11. G. Guichard, I. Huc, Chem. Commun. 47, 5933–5941

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ACKNOWLEDGMENTS

The synthesis and structural characterization of this workwas supported by the NSF under award no. DMR-1508731.Experimental work on SAXS was supported by the U.S.Department of Energy (DOE), Office of Science, Office ofBasic Energy Sciences, under award no. DE-FG02-00ER45810.MD simulations were supported by the Center for Bio-InspiredEnergy Science, an Energy Frontier Research Center funded byDOE, Office of Science, Basic Energy Sciences, under awardno. DE-SC0000989 (T.Y. and G.C.S.). We thank A. Koltonowfor help with AFM measurements and M. Seniw for help withthe preparation of graphics. We also acknowledge S. Kewalramanifor helpful discussions on the SAXS data. Use of theAdvanced Photon Source (APS) was supported by DOE,Office of Science, Office of Basic Energy Sciences, undercontract no. DE-AC02-06CH11357. SAXS experiments wereperformed at the DuPont–Northwestern–Dow CollaborativeAccess Team (DND-CAT) located at Sector 5 of APS.DND-CAT is supported by E. I. DuPont de Nemours andCo., The Dow Chemical Company, and Northwestern University.We thank the Biological Imaging Facility at Northwesternand the Electron Probe Instrumentation Center facilities ofthe Northwestern University Atomic and NanoscaleCharacterization Experimental Center for the use of TEM.Nuclear magnetic resonance and MS equipment at theIntegrated Molecular Structure Education and ResearchCenter was supported by the NSF under grant no. CHE-9871268.We are also grateful to the Peptide Synthesis Core at theSimpson Querrey Institute for BioNanotechnology and KeckBiophysics Facility for instrument use.

SUPPLEMENTARY MATERIALS

www.sciencemag.org/content/351/6272/497/suppl/DC1Materials and MethodsSupplementary TextSchemes S1 to S3Figs. S1 to S23Table S1References (28–38)

9 September 2015; accepted 31 December 201510.1126/science.aad4091

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Simultaneous covalent and noncovalent hybrid polymerizationsZhilin Yu, Faifan Tantakitti, Tao Yu, Liam C. Palmer, George C. Schatz and Samuel I. Stupp

DOI: 10.1126/science.aad4091 (6272), 497-502.351Science 

, this issue p. 497Sciencecatalyze the covalent polymerization.stepwise, lower-molecular-weight flat tapes formed instead, which suggests that supramolecular interactions helped towhen three monomers react, two covalently and one in a supramolecular fashion. When the reaction proceeded

report the synthesis of cylindrical fiberset al.through weaker supramolecular interactions such as hydrogen bonds. Yu In biology, structural polymers such as cytoskeletal fibers assemble from covalently polymerized monomers

Doubling down on polymerization

ARTICLE TOOLS http://science.sciencemag.org/content/351/6272/497

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