In this paper, we present a study of a series of carbon-supported Pd−Sn binary alloyed catalysts prepared through a modified Polyol method as anode electrocatalysts for direct ethanol fuel cell reactions in an alkaline medium. Transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and aberration-corrected scanning transmission electron microscopy equipped with electron energy loss spectroscopy were used to characterize the Pd−Sn/C catalysts, where homogeneous Pd−Sn alloys were determined to be present with the surface Sn being partially oxidized. Among various Pd−Sn catalysts, Pd 86 Sn 14 /C catalysts showed much enhanced current densities in cyclic voltammetric and chronoamperometric measurements, compared to commercial Pd/C (Johnson Matthey). The overall rate law of ethanol oxidation reaction for both Pd 86 Sn 14 /C and commercial Pd/C were also determined, which clearly showed that Pd 86 Sn 14 /C was more favorable in high ethanol concentration and/or high pH environment. Density functional theory calculations also confirmed Pd−Sn alloy structures would result in lower reaction energies for the dehydrogenation of ethanol, compared to the pure Pd crystal.

The breast tumor microenvironment (TMEN) is a unique niche where protein fibers help to promote invasion and metastasis. Cells migrating along these fibers are constantly interacting with each other. How cells respond to these interactions has important implications. Cancer cells that circumnavigate or slide around other cells on protein fibers take a less tortuous path out of the primary tumor; conversely, cells that turn back upon encountering other cells invade less efficiently. The contact response of migrating cancer cells in a fibrillar TMEN is poorly understood. Here, using high-aspect ratio micropatterns as a model fibrillar platform, we show that metastatic cells overcome spatial constraints to slide effectively on narrow fiber-like dimensions, whereas nontransformed MCF-10A mammary epithelial cells require much wider micropatterns to achieve moderate levels of sliding. Downregulating the cell-cell adhesion protein, E-cadherin, enables MCF-10A cells to slide on narrower micropatterns; meanwhile, introducing exogenous E-cadherin in metastatic MDA-MB-231 cells increases the micropattern dimension at which they slide. We propose the characteristic fibrillar dimension (CFD) at which effective sliding is achieved as a metric of sliding ability under spatial confinement. Using this metric, we show that metastasis-promoting genetic perturbations enhance cell sliding and reduce CFD. Activation of ErbB2 combined with downregulation of the tumor suppressor and cell polarity regulator, PARD3, reduced the CFD, in agreement with their cooperative role in inducing metastasis in vivo. The CFD was further reduced by a combination of ErbB2 activation and transforming growth factor β stimulation, which is known to enhance invasive behavior. These findings demonstrate that sliding is a quantitative property and a decrease in CFD is an effective metric to understand how multiple genetic hits interact to change cell behavior in fibrillar environments. This quantitative framework sheds insights into how genetic perturbations conspire with fibrillar maturation in the TMEN to drive the invasive behavior of cancer cells.

Epithelial-mesenchymal transition (EMT) is a complex process by which cells acquire invasive properties that enable escape from the primary tumor. Complete EMT, however, is not required for metastasis: circulating tumor cells exhibit hybrid epithelial-mesenchymal states, and genetic perturbations promoting partial EMT induce metastasis in vivo. An open question is whether and to what extent intermediate stages of EMT promote invasiveness. Here, we investigate this question, building on recent observation of a new invasive property. Migrating cancer cell lines and cells transduced with prometastatic genes slide around other cells on spatially confined, fiberlike micropatterns. We show here that low-dosage/short-duration exposure to transforming growth factor beta (TGFb) induces partial EMT and enables sliding on narrower (26 mm) micropatterns than untreated counterparts (41 mm). High-dosage/long-duration exposure induces more complete EMT, including disrupted cell-cell contacts and reduced E-cadherin expression, and promotes sliding on the narrowest (15 mm) micropatterns. These results identify a direct and quantitative relationship between EMT and cell sliding and show that EMT-associated invasive sliding is progressive, with cells that undergo partial EMT exhibiting intermediate sliding behavior and cells that transition more completely through EMT displaying maximal sliding. Our findings suggest a model in which fiber maturation and EMT work synergistically to promote invasiveness during cancer progression.

Juxtacrine cell-cell signaling mediated by the direct interaction of adjoining mammalian cells is arguably the mode of cell communication that is most recalcitrant to engineering. Overcoming this challenge is crucial for progress in biomedical applications, such as tissue engineering, regenerative medicine, immune system engineering and therapeutic design. Here, we describe the significant advances that have been made in developing synthetic platforms (materials and devices) and synthetic cells (cell surface engineering and synthetic gene circuits) to modulate juxtacrine cell-cell signaling. In addition, significant progress has been made in elucidating design rules and strategies to modulate juxtacrine signaling based on quantitative, engineering analysis of the mechanical and regulatory role of juxtacrine signals in the context of other cues and physical constraints in the microenvironment. These advances in engineering juxtacrine signaling lay a strong foundation for an integrative approach to utilizing synthetic cells, advanced ‘chassis’ and predictive modeling to engineer the form and function of living tissues.

In a crowded, fibrillar tumor microenvironment (TMEN), invading cancer cells encounter and interact with many other cells and cell types. Whether cancer cells stop migrating or reverse direction at every encounter with another cell, or circumnavigate and slide around the encounter, will affect the efficiency of the invasion process. We find that breast cancer cells migrating along fiber-like micropatterns (FLMs) respond differently to cell-cell encounters than what is expected based on the classically-established phenotype of contact-inhibition of locomotion (CIL). Cancer cells are remarkable efficient at sliding around other cancer cells, even along FLMs much narrower than their own cell body. In contrast, non-transformed breast epithelial cells reverse direction upon encountering other normal cells. Differences in cell size fail to predict these outcomes. Interestingly, the participation of normal cells in invasive sliding behavior increases when interacting with a cancer cell rather than another a normal cell. This induction of cancer-like behavior in normal cells suggests that heterotypic interactions between disparate cell types in the TMEN may produce synergistic, disease-promoting collective behaviors. Furthermore, using a series of individual and combinatorial genetic perturbations, we show that genetic factors (ErbB2, E-cadherin, PARD3, TGFbeta) quantitatively shift the ability of normal cells to slide. Specifically, successive genetic perturbations enable normal cells to slide on progressively narrower FLMs. These results suggest that as fibers align and mature during cancer progression, coincident genetic perturbations enable cells to take advantage of the widening fibrillar tracks to execute slides and achieve more efficient dispersion in a crowded microenvironment. Citation Format: Daniel Milano, Senthil Muthuswamy, Anand Asthagiri. ‘Touch-and-go' behavior of cancer cells in spatially-confined, fiber-like microenvironments. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A37.