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Vapor-phase, metal-containing organic compounds can diffuse into polymers and modify the material composition and structure. In this work, using a sequential vapor infiltration process based on atomic layer deposition chemistry, we combine in situ Fourier transform infrared transmission and quartz crystal microbalance experiments with ab initio quantum chemical modeling analysis to evaluate and identify likely reaction mechanisms when poly(methyl methacrylate) (PMMA) thin films are exposed to trimethylaluminum (TMA) vapor. We find that TMA readily diffuses into the PMMA, where it physisorbs to ester carbonyl units (C]O) to form a metastable C]O/Al(CH 3 ) 3 adduct structure that desorbs at moderate temperatures (<100 C). The Lewis-acidic TMA withdraws charge from the C]O, shifting its stretching frequency from 1732 cm À1 in untreated PMMA to 1670 cm À1 after TMA exposure. At higher temperatures IR results show a new feature near 1568 cm À1 that is stable, even upon exposure to water vapor, indicating covalent bond formation. Based on known TMA-polymer reaction mechanisms and ab initio model results, we propose that at T > 100 C, TMA reacts with PMMA to form covalent resonant C]O/Al-O-C bonding units, and does not form -O-C-O-Al(CH 3 ) as previously hypothesized. This mechanistic insight will help elucidate other polymer/Lewis-acid vapor reactions and could enable new applications for sequential vapor infiltration processes.

Breast cancer preferentially spreads to the bone, brain, liver, and lung. The clinical patterns of this tissue-specific spread (tropism) cannot be explained by blood flow alone, yet our understanding of what mediates tropism to these physically and chemically diverse tissues is limited. While the microenvironment has been recognized as a critical factor in governing metastatic colonization, the role of the extracellular matrix (ECM) in mediating tropism has not been thoroughly explored. We created a simple biomaterial platform with systematic control over the ECM protein density and composition to determine if integrin binding governs how metastatic cells differentiate between secondary tissue sites. Instead of examining individual behaviors, we compiled large patterns of phenotypes associated with adhesion to and migration on these controlled ECMs. In combining this novel analysis with a simple biomaterial platform, we created an in vitro fingerprint that is predictive of in vivo metastasis. This rapid biomaterial screen also provided information on how β1, α2, and α6 integrins might mediate metastasis in patients, providing insights beyond a purely genetic analysis. We propose that this approach of screening many cell–ECM interactions, across many different heterogeneous cell lines, is predictive of in vivo behavior, and is much simpler, faster, and more economical than complex 3D environments or mouse models. We also propose that when specifically applied toward the question of tissue tropism in breast cancer, it can be used to provide insight into certain integrin subunits as therapeutic targets. Insight, innovation, integration We developed a high-throughput method to rapidly screen cell adhesion, motility, and growth factor responses on biomaterial surfaces. This approach is analogous to systems biology, relying on cell phenotypes in lieu of genetics. We used this technique to reveal patterns of phenotypes associated with breast cancer metastasis to possible tissue sites (bone, brain, lung). By comparing the phenotypic patterns between cell lines that metastasize to only one tissue site with heterogeneous cell lines, we provide the first method to connect in vitro phenotype to in vivo fate. This method is successful without genetic analysis, yet it also predicts outcomes related to integrin gene expression, potentially identifying new targets for tissue-specific metastasis.

The sequential vapor infiltration (SVI) method, based on atomic layer deposition chemistry, allows the creation of a polymer–inorganic hybrid material through the diffusion of metal–organic vapor reagents into a polymer substrate. This study investigates the reactivity of the ester, amide, and carboxylic acid functional groups of poly­(methyl methacrylate) (PMMA), poly­(vinylpyrrolidone) (PVP), and poly­(acrylic acid) (PAA), respectively, in the presence of trimethylaluminum (TMA) vapor. This work explores the possible reaction mechanisms of these functional groups through in situ Fourier transform infrared spectroscopy and ab initio quantum chemical analysis. At temperatures of ≤100 °C, TMA physisorbs to the carbonyl groups of PMMA. As the temperature is increased, TMA forms a covalent bond with PMMA. TMA physisorbs to PVP and then partially desorbs in the presence of water for all studied temperatures of ≤150 °C. PAA readily reacts with TMA to form a covalent bond with the carbonyl group at 60 °C. This increased reactivity is attributed to the acidic proton in the carboxylic acid moiety based on TMA’s reactivity with hydroxyl-terminated surfaces and ab initio calculations. At temperatures of ≥100 °C, TMA catalyzes anhydride formation in PAA. These insights will help with the prediction of chemical interactions in SVI processes for the development of organic–inorganic hybrid materials.