Orthogonal Surface-Grafted Polymer Gradients: A Versatile ... · Orthogonal Surface-Grafted Polymer Gradients: A Versatile Combinatorial Platform RAJENDRA R. BHAT, MICHAEL R. TOMLINSON,

Orthogonal Surface-Grafted Polymer Gradients:A Versatile Combinatorial Platform

RAJENDRA R. BHAT, MICHAEL R. TOMLINSON, JAN GENZER

Department of Chemical & Biomolecular Engineering, North Carolina State University, Raleigh,North Carolina 27695-7905

Received 13 May 2005; revised 20 June 2005; accepted 18 July 2005DOI: 10.1002/polb.20640Published online in Wiley InterScience (www.interscience.wiley.com).

ABSTRACT: Orthogonal polymer brush gradients are assemblies of surface-anchored macromolecules, in which two material properties of the graftedchains (e.g., grafting density, molecular weight) vary independently inorthogonal directions. Here, we describe the formation and applications oftwo such orthogonal assemblies, involving: (1) molecular weight and graftingdensity (MW/r) gradients of a given polymer and (2) molecular weightgradients (MW1/MW2), of two different polymers. Each point on orthogonalgradient substrate represents a unique combination of the two surface prop-erties being varied, thus facilitating systematic investigation of a pheno-menon that depends on the two said properties. We illustrate this point byemploying orthogonal structures to study systematically: (1) formation ofpolymer brush-nanoparticle composite assemblies, (2) protein adsorption andcell adhesion, and (3) chain conformations in tethered diblock copolymers ex-posed to selective solvents. VVC 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym

Phys 43: 3384–3394, 2005

Keywords: combinatorial polymer science; polymer gradient; polymer/nanoparticle

INTRODUCTION

Combinatorial materials research and highthroughput experimentation (HTE) methodsreceived a great deal of academic as well as indus-trial attention in recent years because of theirability to explore systematically a multi-parame-ter phenomenon and enhance data acquisitionspeed and efficiency.1–4 While the primary benefi-ciary of the application of HTE methods has beenthe pharmaceutical industry inundated with alarge number of potential drug candidates that

need to be screened effectively,5 the successfulimplementation of HTE techniques in pharm-aceutical research has triggered the growth ofcombinatorial approaches in materials sciencealso. Specifically, materials such as catalysts,6

electronic and luminescent materials,7 ceramics,and polymers8,9 have witnessed intense researchefforts devoted toward identifying better formula-tions by optimizing a number of system variables.Bulk polymeric systems and thin polymer coat-ings, which are used in a number of industriallyrelevant applications, were rigorously subjectedto HTE to comprehensively map out the struc-ture–property relationship.4,8–11 In this regard,recent efforts in combinatorial materials researchcarried out at the National Institute of Standardsand Technology9,12 and the Dutch Polymer Insti-

Correspondence to: J. Genzer (E-mail: [email protected])

Journal of Polymer Science: Part B: Polymer Physics, Vol. 43, 3384–3394 (2005)VVC 2005 Wiley Periodicals, Inc.

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tute8,10,11 are noteworthy. One major class of thinpolymer films that has not yet been fully exploredby the aforementioned studies pertains to sys-tems involving surface-anchored polymers.13

Grafted polymer films are vital components inmany important applications such as preventionof biofouling, surface modification and pattern-ing, creation of responsive surfaces, improvingstability of colloidal dispersion, enhancing adhe-sion and wettability, etc.13 The performance ofgrafted polymers in these applications is decidedprimarily by their molecular weight (MW), graft-ing density (r ¼ number of polymer chains perunit area of grafted surface), and composition.13

In light of the importance of surface-boundpolymeric systems, we developed multivariategrafted polymer substrates with the overarchinggoal of utilizing these combinatorial substratesfor understanding the behavior of anchored poly-mers and their interaction with foreign materi-als.14 To this end, we created substrates havinggradients in MW,15 r,16 and composition17 ofgrafted polymers, using surface-initiated con-trolled radical polymerization.18 A gradient inr so formed was employed to study mushroom-to-brush crossover in surface-anchored polyacryla-mide (PAAm).19 Similar gradients in r of graftedpoly(acrylic acid) facilitated detailed study of theresponse of end-anchored polyelectrolyte to ionicsolutions.20 Gradient in MW of anchored PAAmwas utilized as templates for assembling goldnanoparticles.21 Number density of particlesattached to PAAm brush was altered by varyingMW of PAAm chain. In another study, spatial dis-tribution of dispersed nanoparticles was controlledthrough the use of polymer assembly having gra-dient in r.22 In these experiments, gradient geome-

try allowed methodical exploration of the effect ofpolymer MW or r, while keeping the other param-eters constant.

Successful application of one-property gradientin providing insight into the complex behavior ofanchored polymers prompted us to construct thesecond generation of combinatorial grafted poly-mer substrate, wherein effect of two independentsystem parameters can be simultaneously stud-ied. For example, one can vary MW along onedirection of the substrate and r along the otherdirection, thus generating a (MW, r) matrix onthe substrate. We call such substrates orthogonalgradients wherein two material properties varycontinuously along two mutually perpendicularsubstrate directions (see Fig. 1). Since these twoproperties are changing continuously, every pos-sible combination of the two properties can beprobed systematically by using such a set-up.Working with orthogonal gradient substrates notonly saves time and resources, but it also mini-mizes the systematic errors associated with car-rying out a large set of individual experiments.Additionally, concurrent variation of the twoproperties facilitates investigation of their coop-erative effect on a given phenomenon. In thisarticle, we describe the formation of two differentorthogonal gradient motifs, involving: (1) molecu-lar weight and grafting density (MW/r) gradientsof a given polymer, and (2) molecular weight gra-dients (MW1/MW2) of two different polymers. Inaddition, we demonstrate how these orthogonalstructures can be utilized to probe systematically:(1) protein adsorption and cell adhesion, and (2)chain conformations of diblock copolymers ex-posed to selective solvents.

Figure 1. Schematic illustrating the concept of an orthogonal gradient. Orthogonalgradients are formed by combining two individual linear gradients, which propagatein two mutually orthogonal directions. Examples of material properties inherent tosurface-bound polymeric systems that can be gradually varied involve (but are notlimited to): molecular weight, grafting density, charge, composition, and so forth.[Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

ORTHOGONAL SURFACE-GRAFTED POLYMER GRADIENTS 3385

MOLECULAR WEIGHT/GRAFTINGDENSITY (MW/r) ORTHOGONALGRADIENT

MWand r determine the conformation of polymerchains on the substrate, which, in turn, governsthe effectiveness of polymer coating for a givenapplication.13 Thus, it is desirable to be able tosystematically manipulate the chain conforma-tion by controlling MWand r of the chains. Fabri-cation of surface-grafted orthogonal gradiententails two steps: (1) formation of concentrationgradient of initiator molecules and (2) growth ofsurface-anchored chains with a MW gradient in adirection perpendicular to that of the initiatorconcentration gradient. Figure 2 depicts the pro-cedure used to construct MW/r orthogonal gra-dient of surface-anchored polymers. First amolecular gradient of the polymerization initiatoris formed on a solid substrate by vapor deposi-

tion23 of n-octyltrichlorosilane followed by solu-tion backfilling with [11-(2-bromo-2-methylpro-pionyloxy) undecyl] trichlorosilane (BMPUS),which acts as an initiator for the atom transferradical polymerization (ATRP). The substrate isthen placed into a polymerization chamber withthe BMPUS gradient positioned horizontally. Thepolymer MW gradient is formed by slowly drain-ing the polymerization mixture using a micro-pump as described in Ref. 15. In Figure 3, we plotthe dry thickness of poly(dimethyl aminoethylmethacrylate) (PDMAEMA) in an orthogonal gra-dient grafted on a flat silica substrate. The data inFigure 3 demonstrate that for a given r, the poly-mer thickness increases upon increasing the MWof PDMAEMA (i.e. moving along the Y-direction).Concurrently, fixing the MW and increasing the r(i.e. moving along the X-direction) also causes anincrease in the film thickness. To study the abilityof the MW/r polymer brush gradients to influence

Figure 2. Schematic illustrating the formation of an orthogonal gradient involvingvariation of molecular weight and grafting density of the surface-anchored polymer.(a) A molecular gradient of n-octyltrichlosilane (OTS) is formed on a silica-coveredsurface, and (b) the empty spaces on the surface are filled with [11-(2-bromo-2-methyl-propionyloxy) undecyl] trichlorosilane (BMPUS). (c) The substrate, with graftedBMPUS gradient positioned horizontally, is placed in the custom-designed polymer-ization chamber and polymer molecular weight gradient is generated using thedraining method, as described in the text. [Color figure can be viewed in the onlineissue, which is available at www.interscience.wiley.com.]

3386 BHAT, TOMLINSON, AND GENZER

the assembly of nanoparticles (citrate-stabilizedgold particles with diameter �17 nm)24 on graftedpolymer surfaces,25 the PDMAEMA orthogonalgradient substrate was simply immersed in goldnanoparticle sol having pH 6.5. At this pH, theelectrostatic interaction between the positivelycharged DMAEMA groups and the citrate groups

adsorbed on the surface of the gold particles causethe nanoparticles to bind to the underlying brush(see Fig. 4). Color of the glass slide in Figure 4changes gradually from light pink (region of lowMW and low r) to dark violet blue (region of highMWand high r) as one moves along the directionsof increasing MW and r. This color change of goldcoating is due to the well-known interparticle plas-mon coupling, which occurs upon crowding of theparticles.26 It is clear that increase in either MWor r results in increased loading of particles on thebrush. In Figure 4(b), we plot visible light absorb-ance spectra collected along r (path A) and MW(path B) gradients. Increase in the intensity ofthe plasmon absorbance peak in the direction ofincreasing MW or r are due to the increasingnumber of particles attached to the polymerchains. The concomitant redshift of the plasmonpeak position suggests intensified interparticleplasmon coupling associated with increase innanoparticle density on the surface. Upon alter-ing r, the color variation is more pronounced forlow MW (shorter) chains relative to longer chains,suggesting that the number of particles bound tothe brush depends on the number of favorable sitesthat particles have access to. Our experimentalresults concerning the effect of increasing MWand r on particle attachment match very wellwith theoretical predictions.27–29

Polymer-coated substrates are used to preventprotein adsorption and thus minimize subsequent

Figure 4. (a) Photograph of a glass slide showing gold nanoparticles bound to anorthogonal gradient of surface grafted PDMAEMA. The color variation along the direc-tion of molecular weight (MW) as well as grafting density (r) gradients indicates differ-ent gold particle uptake along each gradient. (b) Visible light absorbance spectra takenalong (left) red circles (constant molecular MW, r gradient—path A) and (right) greensquares (constant r, gradient MW—path B). [Color figure can be viewed in the onlineissue, which is available at www.interscience.wiley.com.]

Figure 3. Dry thickness of poly(dimethyl amino-ethyl methacrylate) (PDMAEMA) on orthogonalPDMAEMA gradient grafted on a silica substrate.Thickness was measured in a grid of 5 � 5 mm2 on thesubstrate. [Color figure can be viewed in the onlineissue, which is available at www.interscience.wiley.com.]


biofouling.30,31 Polymer chains chemically graftedto the surface 30–36 have been predicted and shownto be more efficient at preventing protein adsorp-tion than physisorbed polymers. Theoretical mod-els revealed the roles of different molecular fea-tures of the grafted polymer in controlling proteinadsorption.37–39 Polymer MW and r have beenpredicted to be two important parameters regulat-ing protein adsorption on a grafted polymer sur-face. 30,31,39,40 While there is no consensus on therelative importance of MWand r in imparting pro-tein resistance to a grafted polymer surface,30,41,42

it has been demonstrated experimentally thatprotein adsorption systematically decreases upon

increasing either MW and/or r of anchoredchains.30,33,36,43 Herein, we utilize our novel poly-mer gradient substrates to manipulate proteinadsorption and consequently tailor the adhesion ofcells.

Recently, we have employed the MW/r polymerbrush gradient for measuring the absorption ofmodel proteins on surfaces.44 Substrates compris-ing orthogonal assemblies of poly(2-hydroxy ethylmethacrylate) (PHEMA) were prepared using theaforementioned method. The adsorption experi-ments were conducted by immersing the PHEMA-coated silica substrates in protein solutions for24 h. Subsequent to this step, the specimens were

Figure 5. (a) (left) Dry thickness of poly(2-hydroxyethyl methacrylate) (PHEMA)brush in an orthogonal gradient as a function of the PHEMA grafting density andmolecular weight. The scale represents the thickness of dry polymer (in nm). (right)Adsorbed amount of fluorescently labeled lysozyme (Lys) as a function of the positionon the orthogonal PHEMA gradient. The scale represents the fluorescence intensity (ina.u.). (b) (left) Dry thickness of PHEMA brush in an orthogonal gradient as a functionof the PHEMA grafting density and molecular weight. The scale represents the thicknessof dry polymer (in nm). (right) Adsorbed amount of fibronectin (FN) as a function of theposition on the orthogonal PHEMA gradient. The scale represents the dry thickness(in nm). The protein dimensions are: Lys (3 � 3 � 4.5 nm3) and FN (60 � 2.5 � 2.5 nm3).[Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]


removed from protein solution, washed with phos-phate buffered saline (PBS) solution and water andthen blow-dried with nitrogen. The adsorbedamount of protein was assessed by either fluores-cent microscopy (when the protein was tagged witha fluorescence dye) or by ellipsometry, which eval-uated the dry thickness of protein layer. In Figure5, we present the results of the adsorption of (a)lysozyme (Lys) and (b) fibronectin (FN) on PHEMAsubstrates. The left part of Figure 5 depicts the drythickness (h) profile of PHEMA on the substrate(darker color indicates thicker polymer layer). Itshould be noted that while the variation of MW islinear along the MW axis, r varies in a nonlinearfashion along r axis. r has diffusion-like profile asvariation in r was achieved through vapor deposi-tion process. The right part of the figure depicts theamount of adsorbed protein (darker color indicatesmore adsorbed protein). As elucidated from fluores-cence microscopy (for Lys) and ellipsometry (forFN) measurements, the amount of protein on thesurface decreased with increasing MW and/or r ofPHEMA on the surface. Upon increasing MW and

r, PHEMA surface coverage increases, as coverageis given by Mr ¼ hqNA, where M is the molecularweight, q is polymer density, and NA is Avogadro’snumber. Hence the data suggest that the amount ofprotein adsorbed depends on the local concentra-tion of the HEMA groups on the surface. Thisobservation is in accord with the calculations ofSzleifer and coworkers31 who predicted that proteinadsorption decreases as surface coverage of pro-tein-resistant polymer increases.

The previous example illustrates that MW/rorthogonal gradients are capable of forming pro-tein density gradients on the surface. Recently,we have utilized this feature to adjust the densityof cells on surfaces.45 FN serves as an anchorfor the attachment of the osteoblastic cells, inparticular, MC3T3-E1, through the amino acidsequence R-G-D (Arg-Gly-Asp) present on the FNmolecule.46–48 MC3T3-E1 osteoblastic cells werecultured on FN-coated gradient substrate usingstandard cell culture protocol. For analysis pur-poses, the cells were stained so as to make thenucleus look blue and the cytoskeleton appear

Figure 6. Contour plots of (a) dry thickness of poly(2-hydroxyethyl methacrylate)(PHEMA) in MW/r orthogonal PHEMA gradient (scale in nm). (b) dry fibronectin(FN) thickness in MW/r orthogonal PHEMA/FN gradient (scale in nm). The scalesdepicting position on the substrate in parts (a) and (b) are in cm. (Top) Images ofMC3T3-E1 cells (nucleus: blue, cytoskeleton/actin: red) cultured on the PHEMA/FNgradient substrates. Images recorded at positions on the sample marked with thenumbers in the bottom panel of the figure.


red. In Figure 6, we plot the dry thickness ofPHEMA in the MW/r sample and the correspond-ing thickness of adsorbed FN. In the upper panelof Figure 6, we present the images of the surfacetaken at various positions along the diagonalupon incubation of cells. Changes in cell densityand morphology are clearly evident. The cell den-sity decreases with increasing PHEMA coverage(decreasing amount of FN) on the surface. Cellmorphology also changes as a function of thePHEMA (and hence FN) coverage. Cells attain apolygonal shape on regions of the substrate cov-ered with large amount of FN and they elongatewhen there is little or no FN present. This behav-ior likely stems from the fact that on thinPHEMA regions, cells find large amount of FN tointeract with, which causes them to spread exten-sively on the surface. However, on thick PHEMAregions cells cannot experience good traction dueto insufficient amount of FN, which causes cellsto stretch out to minimize unfavorable contactswith PHEMA surface. The two examples dis-cussed above illustrate how orthogonal MW/rgradients offer a potent platform that enablessystematic exploration and direct visualization ofthe effects of surface parameters on phenomenaof interest, namely nanocomposite formation andcell adhesion.

‘‘DUAL’’ MOLECULAR WEIGHT (MW1/MW2)ORTHOGONAL GRADIENT

Another orthogonal gradient we are going todescribe here is made of two mutually perpendic-ular linear MW gradients. Such a ‘‘dual’’ MW gra-dient of surface-tethered macromolecules on flatsurfaces (MW1/MW2) can be fabricated by follow-ing the steps depicted in Figure 7. First, a mono-layer of BMPUS, the polymerization initiator, isformed on the specimen and an MW gradient ofpolymer A is formed by the solution drainingmethod. Taking advantage of the fact that thepolymer chains grown by ATRP can be used asmacroinitiators for subsequent polymerization, asecond polymer B can be polymerized on top ofpolymer A. Growing polymer B as an MW gra-dient, using the solution draining method in thedirection perpendicular to the A gradient, resultsin an array of surface-tethered A–B diblockcopolymers with variable lengths of both blocks.Moreover, each spot on the substrate containscopolymer chains that possess a unique combina-tion of the block lengths.

The aforementioned procedure has recently beenapplied to form assemblies of surface-grafted di-block copolymers comprising poly(2-hydroxy ethylmethacrylate) (PHEMA) and poly(methyl metha-crylate) (PMMA) blocks.49 In Figure 8, we plot thedry thicknesses of the (1) PHEMA, (2) PMMAblocks, and (3) the total thickness of PHEMA-b-PMMA copolymer. The thickness of each blockwas determined using ellipsometry after eachsynthesis step. PHEMA dry thickness increaseslinearly along the X direction [horizontal direc-tion in Fig. 8(a)] and the PMMA thicknessincreases linearly in the Y direction [verticaldirection in Fig. 8(b)]. Since r of the chains isapproximately constant on the entire specimen,15

the dry thickness of each block, h, is directly pro-portional to its molecular weight, M (h ¼ rM/qNA, where q and NA are the density and Avoga-

Figure 7. Schematic illustrating the formation of anMW1/MW2 orthogonal gradient involving variation ofmolecular weights of two copolymer blocks on a solidsubstrate. First, a molecular weight gradient of thefirst block is formed on a solid substrate using the solu-tion draining method. The specimen is then rotated by908 and a second block is polymerized using the same solu-tion draining method on top of the substrate-boundmacroinitiator. [Color figure can be viewed in the onlineissue, which is available at www.interscience.wiley.com.]


dro’s number, respectively). As a consequence ofincrease in the MW of both blocks in two orthogo-nal directions, the total PHEMA-b-PMMA copoly-mer thickness varies diagonally across the sam-ple. More information about the various copoly-mer compositions can be obtained by plotting thedry thicknesses of the PHEMA and PMMA blocksalong the various directions indicated by thearrows in Figure 8(c). The horizontally pointingarrows denote copolymers having a constant PMMAlength and a linearly increasing PHEMA length.Two cases are highlighted here, copolymers with ashort (�) and long (�0) PMMA block [Fig. 8(d)].The vertical arrows depict block copolymers with

a linearly varying length of the PMMA block anda constant length of the lower PHEMA block.In Figure 8(e), we mark the boundary casesinvolving a short (�) and long (�0) PHEMA block.The diagonals in Figure 8(c) mark copolymersthat have: (a) approximately constant fraction ofboth blocks, but an increased total length (�),and (b) those with a constant total length but alinearly varying composition (�) [Fig. 8(f)].

In the following example, we demonstrate themerit of such copolymer assemblies with variableblock lengths by exploring the effect of the blocklengths on surface morphology after selective sol-vent treatment. We will validate that these MW1/

Figure 8. Dry thickness profile (in nm) of (a) PHEMA block, (b) PMMA block, and(c) PHEMA-b-PMMA MW1/MW2 orthogonal brush as a function of the position onthe substrate. (d–f) PHEMA (red squares) and total copolymer (blue circles) thick-nesses along the directions depicted in the total thickness profile shown in part c ofthis figure. The cartoons on the top illustrate the PHEMA homopolymer (left) andPHEMA-b-PMMA copolymer (right) brushes grafted on a solid substrate. [Color figurecan be viewed in the online issue, which is available at www.interscience.wiley.com.]


MW2 gradient copolymer motifs represent unpre-cedented combinatorial platform, facilitating sys-tematic and complete characterization of the vari-ous copolymer microstructures that arise as aresult of the solvent exposure. Several research-ers have already reported on utilizing surface-confined copolymer systems in controlling thechain conformations by selectively swelling one ofthe blocks, while collapsing the other. Forinstance, Zhao and coworkers demonstrated thatselective swelling and collapse of poly(styrene-b-methyl methacrylate) brushes produced variablesurface topologies.50,51 This simple method of tai-loring the substrate roughness has led, in recentyears, to some exciting developments in utilizingsurface-grafted polymers as potential ‘‘softvehicles’’ capable of moving nano-sized objects.52

To fully exploit the power of the copolymerbrushes in such applications, one needs to thor-oughly explore the effect of the lengths of the twoblocks and the composition on the brush responseto various stimuli.

We studied the effect of solvent quality byexposing the samples to ethanol, a poor solventfor the PMMA block, and then quickly quenchingby immersing the specimens into liquid ethane.The latter procedure ‘‘freezes’’ the polymer confor-mation, while removing the organic solvent. Thesample surface morphology was then probed withtapping mode atomic force microscopy (AFM). InFigure 9, we plot the morphology diagram based

on multiple AFM scans collected from severalareas on two different PHEMA-b-PMMA orthogo-nal samples. The results reveal that ethanol doesnot affect the sample morphology markedly whenthe PMMA block length is small; the surfacestays predominantly flat (F). However, increasingthe PMMA block length leads to more distinctvariations of the surface topology. First, a transi-tion from flat to micellar (F/M) morphologies isdetected. Upon further increase of PMMA blocklength, the surface micelles (M) become evenmore pronounced. Additional increase in thePMMA block length leads to a transition ofmicelles into more continuous nanostructures (M/C). The continuous (C) topology dominates at thehighest PMMA length investigated. More experi-ments are currently underway to quantitativelyfollow the development of the surface roughnessand the topologies of PHEMA-b-PMMA copoly-mers as a function of various solvents.

Zhulina et al. examined the swelling of sur-face-tethered copolymers by selective solvents,using self-consistent field calculations and scalingarguments.53 Their calculations revealed thatgrafted copolymers exposed to a solvent that is atheta solvent for the bottom block and a poor sol-vent for the top block exhibit several distinct mor-phologies: flat (I), pure B pinned micelles (PMB),A-legged micelles (MAB), star-like micelles (MA),and a bicontinuous phase (BAB). The type of mor-phology the copolymer adopts depends on thelengths of the individual blocks. The trendsobserved in our experiments (see Fig. 9) are inexcellent qualitative agreement with those pre-dicted by Zhulina and coworkers.53–55

CONCLUSIONS AND OUTLOOK

We have demonstrated the application of orthogo-nal polymer brush gradients in understanding (1)the formation of polymer-nanoparticle composite(2) adsorption behavior of biological species suchas proteins and cells, and (3) morphological tran-sitions of surface-anchored copolymers uponexposure to block-selective solvents. We estab-lished that orthogonal gradient surfaces offer fac-ile combinatorial platforms for quick and inex-pensive investigation of a multivariate pheno-menon. Similar study by traditional methodstypically requires preparation of numerous sam-ples, ostensibly under similar experimental condi-tions. The combinatorial methods in this articleobviate such difficulties and enable unambiguous

Figure 9. Morphology diagram of ethanol-quenchedPHEMA-b-PMMA brushes in MW1/MW2 orthogonalsubstrate based on atomic force microscopy (AFM) scansrevealing the existence of flat (F), micellar (M), and con-tinuous (C) morphologies. The edge of each AFM imageis 1 lm long. [Color figure can be viewed in the onlineissue, which is available at www.interscience.wiley.com.]


exploration of the large r and MW space. Sinceorthogonal gradient substrates permit data collec-tion for several combinations of MW and r in onesingle experiment, the variability associated withthese results is likely to be more consistent on agradient sample than that associated with per-forming individual experiments on multiple sam-ples. This is particularly helpful in dealing withsystems comprising biological species, where ex-perimental variation can be very large. Addition-ally, multi-gradient approach allows one to studythe cooperative effects originating from the twodistinct surface properties. The case studies out-lined in this paper have, quite literally, onlyscratched the surface. There are many moreexamples of important scientific and technologicalphenomena that would greatly benefit from utiliz-ing orthogonal gradients. For example, one maythink of applying the concepts of independentlyvarying two material properties of surface-anch-ored polymers to create targets for fast screeningof adsorbates, form surface microsctructures withtailorable size and composition. Another class ofapplications involves using orthogonal gradientsas directional stimulants. For example, by extend-ing the existing body of work employing moleculargradients for guiding motion of liquid drops onsurfaces,23,56–61 orthogonal polymer gradients canbe devised to probe dynamic phenomena on surfa-ces, such as liquid or protein separation, cellmotility, and so forth. One can also combine thevariation in inherent characteristics of graftedpolymers with gradients in other physical proper-ties such as temperature or strain to address signif-icant issues in polymer science.62–64 Clearly, thereis a multitude of possible applications of orthogo-nal structures, with only a few of them listedhere, which will undoubtedly provide a new para-digm for advancing the fundamental understand-ing of structure–property relationship governingmaterial behavior.

We are grateful to the National Science Foundationand the Office of Naval Research for providing finan-cial support for this work. We thank ProfessorRichard Spontak (NCSU Chemical and BiomolecularEngineering, CBE) for his assistance with solvent freez-ing experiments, Professor Gregory Parsons (NCSUCBE) for allowing the generous use of AFM, and JanSinghass (NCSU Glass Shop) for her expertise in theconstruction of polymerization chamber. We thankBryce Chaney, Jon Rowley, and Andrea Liebmann-Vinson (all from Becton Dickinson Technologies, BDT)for collaboration on the cell adsorption studies. MC3T3

cells were kindly provided by Gayle Lester (UNC-Chapel Hill) and Leigh Quarles (Duke University).We thank Chang Chen (BDT) for her help with cellculture maintenance and staining. Fruitful discussionswith many current and past members of the Genzergroup at NCSU are also gratefully acknowledged.

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