H. Heinz, H. Ramezani-Dakhel, Simulations of inorganic-bioorganic interfaces to discover new materials: insights, comparisons to experiment, challenges and opportunities, Chemical Society Reviews, 45, 412-448 (2016).

Natural and man-made materials often rely on functional interfaces between inorganic and organic compounds. Examples include skeletal tissues and biominerals, drug delivery systems, catalysts, sensors, separation media, energy conversion devices, and polymer nanocomposites. Current laboratory techniques are limited to monitor and manipulate assembly on the 1 to 100 nm scale, time-consuming, and costly. Computational methods have become increasingly reliable to understand materials assembly and performance. This review explores the merit of simulations in comparison to experiment at the 1 to 100 nm scale, including connections to smaller length scales of quantum mechanics and larger length scales of coarse-grain models.

C. Yang, M.W. Tibbitt, L. Basta and K.S. Anseth, Mechanical memory and dosing influence stemcell fate, Nature Materials, 13, 645-652 (2014).

We investigated whether stem cells remember past physical signals and whether these can be exploited to dose cells mechanically. We found that the activation of the Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) as well as the pre-osteogenic transcription factor RUNX2 in human mesenchymal stem cells (hMSCs) cultured on soft poly(ethylene glycol) (PEG) hydrogels (Young s modulus E 2 kPa) depended on previous culture time on stiff tissue culture polystyrene (TCPS; E 3 GPa). In addition, mechanical dosing of hMSCs cultured on initially stiff (E 10 kPa) and then soft (E 2 kPa) phototunable PEG hydrogels resulted in either reversible or above a threshold mechanical dose irreversible activation of YAP/TAZ and RUNX2. We also found that increased mechanical dosing on supraphysiologically stiff TCPS biases hMSCs towards osteogenic differentiation. We conclude that stem cells possess mechanical memory with YAP/TAZ acting as an intracellular mechanical rheostat that stores information from past physical environments and influences the cells fate.

S. Wang, L.A. Leinwand and K.S. Anseth, The cells and their matrix microenvironment in cardiac valves, Nature Reviews Cardiology, 11, 715-27 (2014).

During every heartbeat, cardiac valves open and close coordinately to control the unidirectional flow of blood. In this dynamically challenging environment, resident valve cells actively maintain homeostasis, but the signalling between cells and their microenvironment is complex. When homeostasis is disrupted and the valve opening obstructed, haemodynamic profiles can be altered and lead to impaired cardiac function. Currently, late stages of cardiac valve diseases are treated surgically, because no drug therapies exist to reverse or halt disease progression. Consequently, investigators have sought to understand the molecular and cellular mechanisms of valvular diseases using in vitro cell culture systems and biomaterial scaffolds that can mimic the extracellular microenvironment. In this Review, we describe how signals in the extracellular matrix regulate valve cell function. We propose that the cellular context is a critical factor when studying the molecular basis of valvular diseases in vitro, and one should consider how the surrounding matrix might influence cell signalling and functional outcomes in the valve. Investigators need to build a systems-level understanding of the complex signalling network involved in valve regulation, to facilitate drug target identification and promote in situ or ex vivo heart valve regeneration.

D.D. McKinnon, D.W. Domaille, J.N. Cha and K.S. Anseth, Covalently adaptable networks as biophysical ECM mimics for cell culture, Advanced Materials, 26, 865-72 (2014).

Covalently crosslinked synthetic hydrogels are especially suitable as tissue engineering scaffolds due to their well-defined and easily tunable biochemical and biophysical properties. In order to enable complex cell functions like ECM deposition, motility, and spreading, a mechanism for crosslink degradation must be engineered into the material; however, the presence of a degradation trigger can complicate the cellular biophysical microenvironment. Furthermore, covalently crosslinked polymers typically produce an elastic material, while native tissues are complex viscoelastic structures. Here, we present a step-growth poly(ethylene glycol) (PEG) hydrogel crosslinked by reversible hydrazone bonds. The macromer components are readily synthesized from commercially available precursors, and the resulting gels form rapidly under physiological conditions and provide a non-toxic matrix that is suitable for cell culture. This material is capable of mimicking aspects of the viscoelastic properties of native tissues, and the dynamic stress relaxing crosslinks permit complex cellular functions to occur while retaining the benefits of traditional covalently crosslinked hydrogels. Taken together, these attributes make hydrazone crosslinked hydrogels a unique tool for designing viscoelastic scaffolds and studying cellular responses to scaffold elasticity.

S.H. Pang, C.A. Schoenbaum, D.K.Schwartz, and J.W. Medlin, Directing reaction pathways by catalyst active-site selection using self-assembled monolayers , Nature Communications, 4, 2448 (2013).

One key route for controlling reaction selectivity in heterogeneous catalysis is to prepare catalysts that exhibit only specific types of sites required for desired product formation. Here we show that alkanethiolate self-assembled monolayers with varying surface densities can be used to tune selectivity to desired hydrogenation and hydrodeoxygenation products during the reaction of furfural on supported palladium catalysts. Vibrational spectroscopic studies demonstrate that the selectivity improvement is achieved by controlling the availability of specific sites for the hydrogenation of furfural on supported palladium catalysts through the selection of an appropriate alkanethiolate. Increasing self-assembled monolayer density by controlling the steric bulk of the organic tail ligand restricts adsorption on terrace sites and dramatically increases selectivity to desired products furfuryl alcohol and methylfuran. This technique of active-site selection simultaneously serves both to enhance selectivity and provide insight into the reaction mechanism.

C.L. Muhich, B.W Evanko, K.C. Weston, P. Lichty, X. Liang, J. Martinek, C.B. Musgrave, and A.W. Weimer, Efficient Generation of H2 by Splitting Water with an Isothermal Redox Cycle, Science, 341(6145), 540-542 (2013).

This groundbreaking work of the Weimer and Musgrave groups was highlighted in a news article.

Abstract: Solar thermal water-splitting (STWS) cycles have long been recognized as a desirable means of generating hydrogen gas (H2) from water and sunlight. Two-step, metal oxide based STWS cycles generate H2 by sequential high-temperature reduction and water reoxidation of a metal oxide. The temperature swings between reduction and oxidation steps long thought necessary for STWS have stifled STWS s overall efficiency because of thermal and time losses that occur during the frequent heating and cooling of the metal oxide. We show that these temperature swings are unnecessary and that isothermal water splitting (ITWS) at 1350 C using the hercynite cycle exhibits H2 production capacity >3 and >12 times that of hercynite and ceria, respectively, per mass of active material when reduced at 1350 C and reoxidized at 1000 C.

T. Gong, B.J. Adzima, N.H. Baker and C.N. Bowman, "Photopolymerization reactions using the photoinitiated copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction," Advanced Materials, 25(14), 2024-2028 (2013). HIGHLIGHTED on the cover of Adv Mat

This work, which was highlighted on the cover of Advanced Materials, continued the work published in Nature Chemistry (v3, p256-259, 2011) described below through the development of a brand new photopolymerization process by which high glass transition temperature polymer networks can be formed. The cover image illustrates the formation of a cross-linked network in the irradiated/light area while unreacted monomer molecules remain in the dark regions.

Abstract: The first bulk photopolymerization of multifunctional alkyne and azide monomers using the CuAAC reaction is successfully carried out from low molecular weight, nonviscous monomer resins. Compared to other traditional step-growth bulk photopolymerization, this approach readily provides crosslinked, high glass transition temperature polymers that incorporate triazole linkages throughout the polymer structure with great temporal control.

P.S. Noonan, R.H. Roberts and D.K. Schwartz, Liquid Crystal Re-orientation Induced by Aptamer Conformational Changes, J. Am. Chem. Soc., 135, 5183-5189 (2013). HIGHLIGHTED as a JACS Spotlight

This work was highlighted as a JACS Spotlight, JACS135, 5475 5476 (2013).

Abstract: Aptamer-ligand binding events, involving small molecule targets, at a surfactant-laden aqueous/liquid crystal (LC) interface were found to trigger a LC reorientation that can be observed in real-time using polarized light. The response was both sensitive and selective: reorientation was observed at target concentrations on the order of the aptamer dissociation constant, but no response was observed in control experiments with target analogues. Circular dichroism and resonance energy transfer experiments suggested that the LC reorientation was due to a conformational change of the aptamer upon target binding. Specifically, under conditions where aptamer-ligand binding induced a conformational change from a relaxed random coil to more intricate secondary structures (e.g., double helix, G-quadruplex), a transition from planar to homeotropic LC orientation was observed. These observations suggest the potential for a label-free LC-based detection system that can simultaneously respond to the presence of both small molecules and nucleic acids.

M.A. Azagarsamy and K.S. Anseth, Wavelength controlled photo-cleavage of multiple proteins for orthogonal and sequential release, Angewandte Chemie, 52, 13803-807 (2013).

On the right wavelength: Photolabile molecular units that undergo photocleavage under light of different wavelengths can be used for the independent release of different dyes/proteins from a single, preloaded storage hydrogel (see scheme). The controlled release of each protein allowed them to be delivered sequentially and at experimenter-determined times.

H. Wang, M.W. Tibbitt, S.J. Langer, L.A. Leinwand and K.S. Anseth, "Hydrogels preserve native phenotypes of valvular fibroblasts through an elasticity-regulated PI3K/AKT pathway, Proceedings of the National Academy of Sciences, 110, 19336-341 (2013).

Valvular interstitial cells (VICs) are the principal cellular component of cardiac valves and maintain normal valve homeostasis. During valvular fibrosis, VICs differentiate into myofibroblasts and stiffen the valve matrix. The results in this report demonstrate that standard techniques of culturing VICs on supraphysiologically stiff, tissue-culture polystyrene cause a dramatic induction of myofibroblast differentiation. In contrast, culturing VICs on soft, poly(ethylene glycol)-based hydrogels preserves the native, quiescent phenotype. A detailed study of VIC mechano-sensing reveals that matrix elasticity elicits pathologic changes in VICs through PI3K/AKT signaling. A more complete understanding of the molecular mechanisms of VIC mechano-biology may facilitate development of novel therapeutics targeting downstream signaling in matrix-stiffness associated diseases, and may be applicable to fibrotic diseases in different tissues.

T.K.Carlisle, E.F.Wiesenauer, G.D.Nicodemus, D.L.Gin, R.D.Noble, Ideal CO2/Light Gas Separation Performance of Poly(vinylimidazolium) Membranes and Poly(vinylimidazolium)-Ionic Liquid Composite Films, Ind. Eng. Chem. Res., 52(3), 1023 1032 (2013).

Six vinyl-based, imidazolium room-temperature ionic liquid (RTIL) monomers were synthesized and photopolymerized to form dense poly(RTIL) membranes. The effect of polymer backbone (i.e., poly(ethylene), poly(styrene), and poly(acrylate)) and functional cationic substituent (e.g., alkyl, fluoroalkyl, oligo(ethylene glycol), and disiloxane) on ideal CO2/N2 and CO2/CH4 membrane separation performance was investigated. The vinyl-based poly(RTIL)s were found to be generally less CO2-selective compared to analogous styrene- and acrylate-based poly(RTIL)s. The CO2 permeability of n-hexyl- (69 barrers) and disiloxane- (130 barrers) substituted vinyl-based poly(RTIL)s were found to be exceptionally larger than that of previously studied styrene and acrylate poly(RTIL)s. The CO2 selectivity of oligo(ethylene glycol)-functionalized vinyl poly(RTIL)s was enhanced, and the CO2 permeability was reduced when compared to the n-hexyl-substituted vinyl-based poly(RTIL). Nominal improvement in CO2/CH4 selectivity was observed upon fluorination of the n-hexyl vinyl-based poly(RTIL), with no observed change in CO2 permeability. However, rather dramatic improvements in both CO2 permeability and selectivity were observed upon blending 20 mol % RTIL (emim Tf2N) into the n-hexyl- and disiloxane-functionalized vinyl poly(RTIL)s to form solid liquid composite films.

I. P. Campbell, C. He, and M. P. Stoykovich, Topologically Distinct Lamellar Block Copolymer Morphologies Formed by Solvent and Thermal Annealing , ACS Macro Letters, 2 (10), 918-923 (2013).

This research on solvent annealing of block copolymer thin films was featured on the cover of ACS Macro Letters.

Abstract: Solvent annealing produces ordered assemblies in thin films of block copolymers and, in contrast to uniform thermal annealing, can be used to tune the self-assembled morphology, control the domain orientation with respect to the substrate, and, as demonstrated here, reduce the defect density. The two-dimensional network topology of lamellae self-assembled by polystyrene-block-poly(methyl methacrylate) block copolymers in thin films was compared when processed by solvent and thermal annealing techniques. The mixed solvent annealing method described here reduced the overall defect density (e.g., dislocations with PMMA or PS cores) and thus the connectivity of the lamellar domains compared to thermal annealing; however, the long-range continuity of the networks was maintained and depended primarily on the copolymer composition. In addition, the persistence length of the lamellar domains for solvent annealed films was found to be 2 3 times that of the corresponding thermally annealed systems.

M.J. Skaug, J. Mabry and D.K. Schwartz, Intermittent Molecular Hopping at the Solid-Liquid Interface, Physical Review Letters, 110, 256101 (2013).

The mobility of molecules on a solid surface plays a key role in diverse phenomena such as friction and self-assembly and in surface-based technologies like heterogeneous catalysis and molecular targeting. To understand and control these surface processes, a universally applicable model of surface transport at solid-liquid interfaces is needed. However, unlike diffusion at a solid-gas interface, little is known about the mechanisms of diffusion at a solid-liquid interface. Using single-molecule tracking at a solid-liquid interface, we found that a diverse set of molecules underwent intermittent random walks with non-Gaussian displacements. This contrasts with the normal random walk and Gaussian statistics that are commonly assumed for molecular surface diffusion. The molecules became temporarily immobilized for random waiting times between surface displacements produced by excursions through the bulk fluid. A common power-law distribution of waiting times indicated a spectrum of binding energies. We propose that intermittent hopping is universal to molecular surface diffusion at a solid-liquid interface.

T. Martin, P. Dodd and A. Jayaraman, "Polydispersity for Tuning the Potential of Mean Force between Polymer Grafted Nanoparticles in a Polymer Matrix", Phys. Rev. Lett., 110, 018301 (2013).

We present an integrated theory and simulation study of polydisperse polymer grafted nanoparticles in a polymer matrix to demonstrate the effect of polydispersity in graft length on the potential of mean force between the grafted nanoparticles. In dense polymer solutions, increasing polydispersity in graft length reduces the strength of repulsion at contact and weakens the attractive well at intermediate interparticle distances, completely eliminating the latter at high polydispersity index. The reduction in contact repulsion is attributable to polydispersity relieving monomer crowding near the particle surface, especially at high grafting densities. The elimination of the midrange attractive well is attributable to the longer grafts in the polydisperse graft length distribution that introduce longer range steric repulsion and alter the wetting of the grafted layer by matrix chains. Dispersion of the grafted particles is stabilized by increased penetration or wetting of the polydisperse grafted layer by the matrix chains. This work demonstrates that at high grafting densities, polydispersity in graft length can be used to stabilize dispersions of grafted nanoparticles in a polymer matrix at conditions where monodisperse grafts would cause aggregation.

P.T. Nguyen, E.F. Wiesenauer, D.L. Gin, and R.D. Noble, Effect of Composition and Nanostructure on CO2/Light Gas Transport Properties of Supported Alkyl-imidazolium Block Copolymer Membranes, J. Membr. Sci. 430, 312 320 (2013).

Polymerized room-temperature ionic liquids (poly(RTIL)s) have garnered attention as new and interesting membrane materials for CO2/light gas separations because they combine the high CO2 affinity and thermal and chemical stability of RTILs, with the physical and mechanical properties of polymeric materials. Our group recently synthesized a new type of block copolymer (BCP) combining an imidazolium-based poly(RTIL) and an alkyl non-ionic polymer. These alkyl-b-ionic BCPs phase-separate into ordered nanostructures. Prior work investigating gas transport through phase-separated BCPs is very limited, and none has included RTIL-based BCP systems. However it has been shown that nanoscale phase-separation could facilitate gas transport via nanostructure orientation control or phase connectivity improvement. We have successfully made defect-free, thin-film composite membranes with these novel alkyl-imidazolium BCPs as a 3 20 m thick top layer, and determined their CO2/N2 separation properties via single-gas permeability measurements and selectivity calculations. These new BCP materials were found to have distinct advantages over the analogous physical blends of the parent homopolymers with respect to membrane fabrication. The composition of the BCP top layer, which is directly connected to the type of nanostructure formed, was found to have a significant effect on CO2 permeability (i.e., it can increase CO2 permeability by two orders of magnitude up to an observed value of 9300barrer). This improvement is mainly due to a large increase in the diffusion coefficient in the ordered nanostructures compared to amorphous BCP materials.

C.A. DeForest and K.S. Anseth, Photoreversible patterning of biomolecules within click-based hydrogels, Angewandte Chemie, 51, 1816-19 (2012).

This article was featured on the back cover of Angewandte Chemie.

Reversible biomolecular patterning in hydrogels can direct cell function in a user-defined manner. In their communication on page 1816 ff., K. S. Anseth and C. A DeForest report 4D spatiotemporal control over the presentation of bioligands by using a thiol ene photoconjugation reaction, which is initiated by visible light, combined with the photocleavage of an o-nitrobenzyl ether, which is controlled by UV light. This method allows cell functions to be probed dynamically.

M.W. Tibbitt and K.S. Anseth, Dynamic environments: The fourth dimension, Science Translational Medicine, 4, 160ps24 (2012).

The extracellular space, or cell microenvironment, choreographs cell behavior through myriad controlled signals, and aberrant cues can result in dysfunction and disease. For functional studies of human cell biology or expansion and delivery of cells for therapeutic purposes, scientists must decipher this intricate map of microenvironment biology and develop ways to mimic these functions in vitro. In this Perspective, we describe technologies for four-dimensional (4D) biology: cell-laden matrices engineered to recapitulate tissue and organ function in 3D space and over time.

M. Kastantin, R. Walder and D.K. Schwartz, Identifying Mechanisms of Interfacial Dynamics Using Single-Molecule Tracking, Langmuir, 28, 12443-12456 (2012). FEATURE ARTICLE

The soft (i.e., noncovalent) interactions between molecules and surfaces are complex and highly varied (e.g., hydrophobic, hydrogen bonding, and ionic), often leading to heterogeneous interfacial behavior. Heterogeneity can arise either from the spatial variation of the surface/interface itself or from molecular configurations (i.e., conformation, orientation, aggregation state, etc.). By observing the adsorption, diffusion, and desorption of individual fluorescent molecules, single-molecule tracking can characterize these types of heterogeneous interfacial behavior in ways that are inaccessible to traditional ensemble-averaged methods. Moreover, the fluorescence intensity or emission wavelength (in resonance energy transfer experiments) can be used to track the molecular configuration and simultaneously directly relate this to the resulting interfacial mobility or affinity. In this feature article, we review recent advances involving the use of single-molecule tracking to characterize heterogeneous molecule surface interactions including multiple modes of diffusion and desorption associated with both internal and external molecular configuration, Arrhenius-activated interfacial transport, spatially dependent interactions, and many more.

Y.C. Hudiono, A.L. Miller II, P.W. Gibson, A.L. LaFrate, R.D. Noble, and D.L. Gin, A Highly Breathable Organic-Inorganic Barrier Material that Blocks the Passage of Blister Agent Simulants, Ind. Eng. Chem. Res., 51(21), 7453 7456 (2012).

Garment materials that provide protection against exposure to toxic chemical warfare agents (CWAs) not only require the ability to block the passage of these toxic compounds in vapor form but also the ability to transport water vapor to allow cooling for the wearer. Only a very limited number of examples of such breathable CWA barrier materials are known. A new type of reactive organic/inorganic composite film material is presented that has a very high water vapor transport rate (>1800 g m^ 2 day^ 1 for a 220- m-thick film) and the ability to completely block penetration of the mustard agent simulant, 2-chloroethyl ethyl sulfide (CEES), after 22 h of continuous exposure. This new composite material is based on two components: (1) a cross-linked, diol-functionalized room-temperature ionic liquid polymer that serves as a dense, flexible hydrophilic matrix, and (2) a basic zeolite (sodium zeolite-Y (NaY)) that serves as an inexpensive, nucleophilic additive that chemically degrades the CEES as it enters the film. Preliminary FT-IR studies on this new reactive barrier material suggest that the OH groups on the ionic polymer not only facilitates water vapor transport but may also help activate mustard-type vapors for reaction with the imbedded NaY.

B.A. Voss, R.D. Noble and D.L. Gin, Ionic Liquid Gel-Based Containment and Decontamination Coating for Blister Agent-Contacted Substrates, Chem. Mater. 24(6), 1174 1180 (2012).

Current methods to contain and decontaminate materials contacted by toxic chemical warfare agents (CWAs) have disadvantages with respect to ease of delivery, portability, and effectiveness on porous substrates. A portable, easy-to-use, spreadable coating that immediately acts as a barrier to contain CWA vapors on contacted substrates and also decontaminates soaked-in CWAs is highly desired. A new type of decontaminating barrier coating for sulfur mustard (i.e., blister agent) CWAs has been developed that is made of (1) a spreadable nonvolatile, fluid matrix based on a room-temperature ionic liquid (RTIL), (2) an organic gelator that acts as a solidifying agent to help the applied coating adhere to and prevent runoff from angled or vertical surfaces, and (3) a polyamine that acts as a reagent to chemically degrade and help draw out adsorbed blister agent. When applied to porous and nonporous substrates contacted with 2-chloroethyl ethyl sulfide (CEES, a mustard agent simulant), this spreadable, soft solid coating was found to act as an effective barrier, blocking 70 90% of the CEES vapor from entering the overhead space compared to uncoated samples. Furthermore, this reactive gel RTIL coating was able to remove (i.e., draw out and degrade) 70 95% of the liquid CEES soaked into porous substrates after 24 h at ambient temperature when applied as a static, single-application coating. Preliminary studies with added dyes and indicators to this coating system have shown that the decontamination process may be followed visually via color changes.

B.M.Carter, B.R.Wiesenauer, E.S.Hatakeyama, J.L.Barton, R.D.Noble, D.L.Gin, Glycerol-based Bicontinuous Cubic Lyotropic Liquid Crystal Monomer System for the Fabrication of Thin-film Membranes with Uniform Nanopores Chem. Mater. 24(21), 4005 4007 (2012)

In summary, a new glycerol-based LLC monomer system has been developed that enables facile fabrication of unprecedented TFC QI membranes that have molecular sieving capabilities, high salt rejection, and good water permeability. We are currently exploring methods to reduce the thickness of the 3/glycerol layers to 0.3 m and increase flux by optimizing roll-casting and support parameters, as well as by using other solution processing techniques (e.g., dip-, spray-, and spin-coating). We are also exploring methods for varying the QI pore size, such as the use of cosurfactants, different anions, and mixtures of LLC solvents.

C.J. Kloxin, T.F. Scott, H.Y. Park, and C.N. Bowman, Mechanopatterning on a Photoresponsive Elastomer, Advanced Materials, 23(17), 1977-1981 (2011). FEATURED in Nature

Mechanophotopatterning on a photoresponsive elastomer was demonstrated by Bowman and coworkers, enabling for the first time the ability to precisely and simultaneously manipulate both the material s shape and surface topography by exposure to light without the need for solvents, molding, or physical contact.

This work was featured in a Nature News and Views article by Prof. Huck 472 (7344) 425 (2011).

Photopatterning of a photoreversible cova lent elastomeric network under mechanical strain, or mechanophotopatterning, provides a facile approach to fabricate complex topographical features using elementary irradiation schemes. A photoresponsive material is deformed in two dimensions and irradiated through a mask, resulting in a transparent material with topography that reflects the concentric rings of the mask.

R. Walder, N. Nelson and D.K. Schwartz, Super-Resolution Surface Mapping using the Trajectories of Molecular Probes, Nature Communications, 2, 515 (2011). HIGHLIGHTED in MRS Bulletin

This work was highlighted in the MRS Bulletin, 37, 105 (2012).

Abstract: The surface characterization of 'soft' materials presents a significant scientific challenge, particularly under 'wet' in situ conditions where a wide variety of non-covalent interactions may be relevant. Here we introduce a new chemical imaging method, MAPT (mapping using accumulated probe trajectories) that generates images of surface interactions by distributing different aspects of molecular probe trajectories into distinct locations and then combining many trajectories to generate spatial maps. The maps are super-resolution in nature, because they are accumulated from highly localized single-molecule observations. Unlike other super-resolution techniques, which report only photon or point counts, our analysis generates spatial maps of physical quantities (adsorption rate, desorption probability, local surface diffusion coefficient, surface coverage/occupancy) that are directly associated with the molecular interactions between the probe molecule and the surface. We demonstrate the feasibility of this characterization using a surface patterned with various degrees of hydrophobicity.

B.J. Adzima, Y. Tao, C.J. Kloxin, C.A. DeForest, K.S. Anseth, and C.N. Bowman, Spatial and temporal control of the alkyne azide cycloaddition by photoinitiated Cu(II) reduction, Nature Chemistry, 3, 256 259 (2011).

Bowman et al. developed a method for catalyzing the copper catalyzed azide alkyne cycloaddition using conventional photoinitiators to reduce Cu(II) to Cu(I). Unlike, previous methodologies this approach allows the selective patterning of the reaction using standard photolithographic techniques.


The click reaction paradigm is focused on the development and implementation of reactions that are simple to perform while being robust and providing exquisite control of the reaction and its products. Arguably the most prolific and powerful of these reactions, the copper-catalysed alkyne-azide reaction (CuAAC) is highly efficient and ubiquitous in an ever increasing number of synthetic methodologies and applications, including bioconjugation, labelling, surface functionalization, dendrimer synthesis, polymer synthesis and polymer modification. Unfortunately, as the Cu(I) catalyst is typically generated by the chemical reduction of Cu(II) to Cu(I), or added as a Cu(I) salt, temporal and spatial control of the CuAAC reaction is not readily achieved. Here, we demonstrate catalysis of the CuAAC reaction via the photochemical reduction of Cu(II) to Cu(I), affording comprehensive spatial and temporal control of the CuAAC reaction using standard photolithographic techniques. Results reveal the diverse capability of this technique in small molecule synthesis, patterned material fabrication and patterned chemical modification.

C.A. DeForest and K.S. Anseth, Cytocompatible click-based hydrogels with dynamically-tunable properties through orthogonal photoconjugation and photocleavage reactions, Nature Chemistry, 3, 925-31 (2011).

To provide insight into how cells receive information from their external surroundings, synthetic hydrogels have emerged as systems for assaying cell function in well-defined microenvironments where single cues can be introduced and subsequent effects individually elucidated. However, as answers to more complex biological questions continue to be sought, advanced material systems are needed that allow dynamic alteration of the three-dimensional cellular environment with orthogonal reactions that enable multiple levels of control of biochemical and biomechanical signals. Here, we seek to synthesize one such three-dimensional culture system using cytocompatible and wavelength-specific photochemical reactions to create hydrogels that allow orthogonal and dynamic control of material properties through independent spatiotemporally regulated photocleavage of crosslinks and photoconjugation of pendant functionalities. The results demonstrate the versatile nature of the chemistry to create programmable niches to study and direct cell function by modifying the local hydrogel environment.

C. Lin and K.S. Anseth, Cell-cell communication mimicry with PEG hydrogels for enhancing beta-cell function, Proceedings of the National Academy of Sciences, 108, 6380-85 (2011).

A biomimetic hydrogel platform was designed to signal encapsulated cells using immobilized cell cell communication cues, with a focus on enhancing the survival and function of encapsulated pancreatic -cells to treat type 1 diabetes. When MIN6 cells, a pancreatic -cell line, were encapsulated in poly(ethylene glycol) (PEG) hydrogels, their survival and glucose responsiveness to insulin were highly dependent on the cell-packing density. A minimum packing density of 10^7 cells/mL was necessary to maintain the survival of encapsulated -cells without the addition of material functionalities (e.g., cell adhesion ligands). While single cell suspensions can improve diffusion-limited mass transfer, direct cell cell interactions are limited. Thus, thiolated EphA5-Fc receptor and ephrinA5-Fc ligand were conjugated into PEG hydrogels via a thiol-acrylate photopolymerization to render an otherwise inert PEG hydrogel bioactive. The biomimetic hydrogels presented here can provide crucial cell cell communication signals for dispersed -cells and improve their survival and proliferation. Together with the cell-adhesive peptide RGDS, the immobilized fusion proteins (EphA5-Fc and ephrinA5-Fc) synergistically increased the survival of both MIN6 -cells and dissociated islet cells, both at a very low cell-packing density (< 2   10^6 cells/mL). This unique gel platform demonstrates new strategies for tailoring biomimetic environments to enhance the encapsulation of cells that require cell cell contact to survive and function.

R. Walder, N. Nelson and D.K. Schwartz, Single Molecule Observations of Desorption-Mediated Diffusion at the Solid-Liquid Interface, Physical Review Letters, 107, 156102 (2011). HIGHLIGHTED in Virtual Journal of Biological Physics

By directly observing molecular trajectories on a chemically heterogeneous surface, we have identified two distinct modes of diffusion involving (1) displacements within isolated surface islands (crawling mode), and (2) displacements where a molecule desorbs from an island, diffuses through the adjacent liquid phase, and readsorbs on another island (flying mode). The diffusion coefficients corresponding to these two modes differ by an order of magnitude, and both modes are also observed on chemically homogeneous surfaces. Comparison with previous results suggested that desorption-mediated diffusion is the primary transport mechanism in self-assembled monolayer formation.


M. Yu, J.L. Falconer and R.D. Noble, Hydrogen Separation Using Defect-Free, Inorganic Composite Membranes J. American Chemical Society, 133, 1748-1750 (2011).

Defect-free, microporous Al2O3/SAPO-34 zeolite composite membranes were prepared by coating hydrothermally grown zeolite membranes with microporous alumina using molecular layer deposition. These inorganic composite membranes are highly efficient for H2 separation: their highest H2/N2 mixture selectivity was 1040, in contrast with selectivities of 8 for SAPO-34 membranes. The composite membranes were selective for H2 for temperatures up to at least 473 K and feed pressures up to at least 1.5 MPa; at 473 K and 1.5 MPa, the H2/N2 separation selectivity was 750. The H2/CO2 separation selectivity was lower than the H2/N2 selectivity and decreased slightly with increasing pressure; the selectivity was 20 at 473 K and 1.5 MPa. The high H2 selectivity resulted either because most of the pores in the Al2O3 layer were slightly smaller than 0.36 nm (the kinetic diameter of N2) or because the Al2O3 layer slightly narrowed the SAPO-34 pore entrance. These composite membranes may represent a new class of inorganic membranes for gas separation.

C.M Donahue, C.M Hrenya, R.H. Davis, "Stokes s Cradle: Newton s Cradle with Liquid Coating," Phys. Rev. Lett., 105, 034501 (2010). FEATURED in Nature

This work was featured in Nature, "Sticky balls," 466, 417 (2010).

Abstract: Granular flows involving liquid-coated solids are ubiquitous in nature (pollen capture, avalanches) and industry (filtration, pharmaceutical mixing). In this Letter, three-body collisions between liquid-coated spheres are investigated experimentally using a Stokes s cradle, which resembles the popular desktop toy Newton s cradle (NC). Surprisingly, previous work shows that every possible outcome was observed in the Stokes s cradle except the traditional NC outcome. Here, we experimentally achieve NC via guidance from a theory, which revealed that controlling the liquid-bridge volume connecting two target particles is the key in attaining the NC outcome. These three-body experiments also provide direct evidence that the fluid resistance upon rebound cannot be completely neglected due to presumed cavitation; this resistance also influences two-body systems yet cannot be isolated experimentally in such systems.

C.E. Hoyle and C.N. Bowman, Thiol-Ene Click Chemistry, Angewandte Chemie International Edition, 49, 1540-1573 (2010).

Professor Bowman co-authored this seminal review on the analysis, mechanism, and various implementations of the thiol-ene click reactions. This article, with 425 citations in just over three years, stands as one of the top 5 most cited articles from among more than 80,000 articles published in the chemistry field since 2010.

Abstract: Following Sharpless visionary characterization of several idealized reactions as click reactions, the materials science and synthetic chemistry communities have pursued numerous routes toward the identification and implementation of these click reactions. Herein, we review the radical-mediated thiol ene reaction as one such click reaction. This reaction has all the desirable features of a click reaction, being highly efficient, simple to execute with no side products and proceeding rapidly to high yield. Further, the thiol ene reaction is most frequently photoinitiated, particularly for photopolymerizations resulting in highly uniform polymer networks, promoting unique capabilities related to spatial and temporal control of the click reaction. The reaction mechanism and its implementation in various synthetic methodologies, biofunctionalization, surface and polymer modification, and polymerization are all reviewed.

S.T. Marshall, M. O Brien, B. Oetter, A. Corpu, R.M. Richards, D.K. Schwartz, and J.W. Medlin, Controlled Selectivity for Palladium Catalysts using Self-assembled Monolayers, Nature Materials, 9, 853-858 (2010).

The selective reaction of one part of a bifunctional molecule is a fundamental challenge in heterogeneous catalysis and for many processes including the conversion of biomass-derived intermediates. Selective hydrogenation of unsaturated epoxides to saturated epoxides is particularly difficult given the reactivity of the strained epoxide ring, and traditional platinum group catalysts show low selectivities. We describe the preparation of highly selective Pd catalysts involving the deposition of n-alkanethiol self-assembled monolayer (SAM) coatings. These coatings improve the selectivity of 1-epoxybutane formation from 1-epoxy-3-butene on palladium catalysts from 11 to 94% at equivalent reaction conditions and conversions. Although sulphur species are generally considered to be indiscriminate catalyst poisons, the reaction rate to the desired product on a catalyst coated with a thiol was 40% of the rate on an uncoated catalyst. Interestingly the activity decreased for less-ordered SAMs with shorter chains. The behaviour of SAM-coated catalysts was compared with catalysts where surface sites were modified by carbon monoxide, hydrocarbons or sulphur atoms. The results suggest that the SAMs restrict sulphur coverage to enhance selectivity without significantly poisoning the activity of the desired reaction.

C.A. DeForest, B.D. Polizzotti and K.S. Anseth, Sequential click reactions for synthesizing and patterning 3D cell microenvironments, Nature Materials, 8, 659-64 (2009).

Click chemistry provides extremely selective and orthogonal reactions that proceed with high efficiency and under a variety of mild conditions, the most common example being the copper(I)-catalysed reaction of azides with alkynes (1,2). While the versatility of click reactions has been broadly exploited (3,4,5), a major limitation is the intrinsic toxicity of the synthetic schemes and the inability to translate these approaches into biological applications. This manuscript introduces a robust synthetic strategy where macromolecular precursors react through a copper-free click chemistry (6), allowing for the direct encapsulation of cells within click hydrogels for the first time. Subsequently, an orthogonal thiol ene photocoupling chemistry is introduced that enables patterning of biological functionalities within the gel in real time and with micrometre-scale resolution. This material system enables us to tailor independently the biophysical and biochemical properties of the cell culture microenvironments in situ. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gels with ideal structures that can be photopatterned, and all in the presence of cells.

  • Kolb, H. C., Finn, M. G. & Sharpless, K. B. Click chemistry: Diverse chemical function from a few good reactions. Angew. Chem. Int. Ed. 40, 2004 2021 (2001).
  • Huisgen, R. 1.3-Dipolare Cycloadditionen Ruckschau und Ausblick. Angew. Chem. Int. Ed. 75, 604 637 (1963).
  • Moses, J. E. & Moorhouse, A. D. The growing applications of click chemistry. Chem. Soc. Rev. 36, 1249 1262 (2007).
  • Kolb, H. C. & Sharpless, K. B. The growing impact of click chemistry on drug discovery. Drug Discov. Today 8, 1128 1137 (2003).
  • Hawker, C. J. & Wooley, K. L. The convergence of synthetic organic and polymer chemistries. Science 309, 1200 1205 (2005).
  • Baskin, J. M. et al. Copper-free click chemistry for dynamic in vivo imaging. Proc. Natl Acad. Sci. USA 104, 16793 16797 (2007).

A.M. Kloxin, A.M. Kasko, C.N. Salinas and K.S. Anseth, Photolabile hydrogels for dynamic tuning of physical and chemical properties, Science, 324, 59-63 (2009).

We report a strategy to create photodegradable poly(ethylene glycol) based hydrogels through rapid polymerization of cytocompatible macromers for remote manipulation of gel properties in situ. Postgelation control of the gel properties was demonstrated to introduce temporal changes, creation of arbitrarily shaped features, and on-demand pendant functionality release. Channels photodegraded within a hydrogel containing encapsulated cells allow cell migration. Temporal variation of the biochemical gel composition was used to influence chondrogenic differentiation of encapsulated stem cells. Photodegradable gels that allow real-time manipulation of material properties or chemistry provide dynamic environments with the scope to answer fundamental questions about material regulation of live cell function and may affect an array of applications from design of drug delivery vehicles to tissue engineering systems.

A. Honciuc and D.K. Schwartz, Probing Hydrophobic Interactions using Trajectories of Amphiphilic Molecules at a Hydrophobic/Water Interface, J. Am. Chem. Soc., 131, 5973-5979 (2009).

Individual molecules of fluorophore-labeled alkanoic acids with various chain lengths, BODIPY (CH2)n COOH (abbreviated as fl-Cn), were observed to adsorb and move at the methylated fused silica water interface as a function of temperature using total internal reflection fluorescence microscopy. The statistical analysis of squared-displacement distributions indicated that the molecular trajectories were consistent with a diffusive model involving two intertwined modes. The slower mode, typically responsible for <50% of the molecular diffusion time, had a diffusion coefficient of <0.005 m2/s and could not be distinguished from the apparent motions of immobilized molecules because of the limitations of experimental resolution. The faster mode exhibited diffusion coefficients that increased with temperature for all chain lengths, permitting an Arrhenius analysis. Both the effective activation energies and kinetic prefactors associated with the fast-mode diffusion coefficients increased systematically with chain length for fl-C2 through fl-C10; however, fl-C15 did not follow this trend but instead exhibited anomalously small values of both parameters. These observations were considered in the context of hydrophobic interactions between the adsorbate molecules and the methylated surface in the presence of water. Specifically, it was hypothesized that fl-C2, fl-C4, and fl-C10 adopted primarily extended molecular conformations on the hydrophobic surface. The increases in activation energy and entropy with chain length for these molecules are consistent with a picture of the transition state in which the molecule partially detaches from the surface and exhibits greater conformational freedom. In contrast, the small activation energy and entropy for fl-C15 are consistent with a scenario in which the surface-bound molecule adopts a compact/globular conformation with limited surface contact and conformational flexibility.

M. Yu, H. Funke, J.L. Falconer, and R.D. Noble, High Density, Vertically-Aligned Carbon Nanotube Membranes , ACS Nano, 9, 225-229 (2009).

A method is presented to prepare high-density, vertically aligned carbon nanotube (VA-CNT) membranes. The CNT arrays were prepared by chemical vapor deposition (CVD), and the arrays were collapsed into dense membranes by capillary-forces due to solvent evaporation. The average space between the CNTs after shrinkage was 3 nm, which is comparable to the pore size of the CNTs. Thus, the interstitial pores between CNTs were not sealed, and gas permeated through both CNTs and interstitial pores. Nanofiltration of gold nanoparticles and N2 adsorption indicated the pore diameters were approximately 3 nm. Gas permeances, based on total membrane area, were 1 4 orders of magnitude higher than VA-CNT membranes in the literature, and gas permeabilities were 4 7 orders of magnitude higher than literature values. Gas permeances were approximately 450 times those predicted for Knudsen diffusion, and ideal selectivities were similar to or higher than Knudsen selectivities. These membranes separated a larger molecule (triisopropyl orthoformate (TIPO)) from a smaller molecule (n-hexane) during pervaporation, possibly due to the preferential adsorption, which indicates separation potential for liquid mixtures.