Copper-Graphene Composite (CGC) Conductors: Synthesis, Microstructure, and Electrical Performance.

Improving the electrical performance of copper, the most widely used electrical conductor in the world is of vital importance to the progress of key technologies, including electric vehicles, portable devices, renewable energy, and power grids. Copper-graphene composite (CGC) stands out as the most promising candidate for high-performance electrical conductor applications. This can be attributed to the superior properties of graphene fillers embedded in CGC, including excellent electrical and thermal conductivity, corrosion resistance, and high mechanical strength. This review highlights the recent progress of CGC conductors, including their fabrication processes, electrical performances, mechanisms of copper-graphene interplay, and potential applications.

Breaking the Intrinsic Strength-Ductility Tradeoff in Graphene-Metal Composites.

Small carbon materials, such as graphene, offer excellent mechanical strength. Micro/nano carbon materials are often dispersed into a metal matrix to form bulk composites with mechanical enhancement. Despite technical progress, such composites intrinsically suffer from a trade-off condition between strength and ductility because the load transfer path forms between mechanically strong yet chemically inert micro/nano carbon materials or between the carbon-metal interfaces. In other words, conventional carbon and metal composites become stronger with increasing carbon contents, but the weak interfaces also increase, leading to premature failure. In this regard, crucial advances are presented toward breaking the strength-ductility trade-off condition by utilizing Axially bi-Continuous Graphene-Nickel (ACGN) wires. This innovative ACGN achieves excellent combined strength and ductility-the highest among the current Ni-, Al-, and Cu-based carbon-enhanced metal matrix composites. For example, the ultimate strength and failure strain of 25-µm-diameter ACGN wires are improved by 71.76% and 58.24%, compared to their counterparts. The experimental and theoretical analyses indicate that the graphene-nickel interplay via their axially bi-continuous structure is the main underlying mechanism for the superb mechanical behavior. In specific, the continuous graphene, in addition to effective load-sharing, passivates the free surface of fine wire, forming dislocation pileups along the graphene-nickel interface and, therefore, hindering localized necking.

Topographical depth reveals contact guidance mechanism distinct from focal adhesion confinement.

Cellular response to the topography of their environment, known as contact guidance, is a crucial aspect to many biological processes yet remains poorly understood. A prevailing model to describe cellular contact guidance involves the lateral confinement of focal adhesions (FA) by topography as an underlying mechanism governing how cells can respond to topographical cues. However, it is not clear how this model is consistent with the well-documented depth-dependent contact guidance responses in the literature. To investigate this model, we fabricated a set of contact guidance chips with lateral dimensions capable of confining focal adhesions and relaxing that confinement at various depths. We find at the shallowest depth of 330 nm, the model of focal adhesion confinement is consistent with our observations. However, the cellular response at depths of 725 and 1000 nm is inadequately explained by this model. Instead, we observe a distinct reorganization of F-actin at greater depths in which topographically induced cell membrane deformation alters the structure of the cytoskeleton. These results are consistent with an alternative curvature-hypothesis to explain cellular response to topographical cues. Together, these results indicate a confluence of two molecular mechanisms operating at increased induced membrane curvature that govern how cells sense and respond to topography.

A 3D printed tensile testing system for micro-scale specimens.

Mechanical property characterization of micro-scale material systems, such as free-standing films or small diameter wires (<20 µm), often requires expensive, specialized test systems. Conventional tensile test systems are usually designed for millimeter scale specimens with the force sensing capability of >1N while microdevice-based testers are intended for micro-/nano-scale specimens operating within a much smaller force range of <10 mN. This disparity leaves a technology gap in reliable and cost-effective characterization methods for specimens at the intermediate scale. In this research, we introduce the cost-effective and all-in-one tensile testing system with a built-in force sensor, self-aligning mechanisms, and loading frames. Owing to the advantages of 3D printing technologies, the ranges of force measurement (0.001-1 N) and displacement (up to tens of millimeters) of our 3D printed tensile tester can be readily tailored to suit specific material dimension and types. We have conducted a finite element simulation to identify the potential sources of the measurement error during tensile testing and addressed the dominant errors by simply modifying the dimension/design of the loading frames. As a proof-of-concept demonstration, we have characterized fine copper (Cu) wires with 10-25 µm diameters by the 3D printed tensile tester and confirmed that the measured mechanical properties match with the known values of bulk Cu. Our work shows that the proposed 3D printed tensile testing system offers a cost-efficient and easily accessible testing method for accurate mechanical characterization of specimens with cross-sectional dimensions of the order of tens of micrometers.

Cavitation nucleation and its ductile-to-brittle shape transition in soft gels under translational mechanical impact.

Cavitation bubbles in the human body, when subjected to impact, are being increasingly considered as a possible brain injury mechanism. However, the onset of cavitation and its complex dynamics in biological materials remain unclear. Our experimental results using soft gels as a tissue simulant show that the critical acceleration (acr) at cavitation nucleation monotonically increases with increasing stiffness of gelatin A/B, while acr for agarose and agar initially increases but is followed by a plateau or even decrease after stiffness reach to ∼100 kPa. Our image analyses of cavitation bubbles and theoretical work reveal that the observed trends in acr are directly linked to how bubbles grow in each gel. Gelatin A/B, regardless of their stiffness, form a localized damaged zone (tens of nanometers) at the gel-bubble interface during bubble growth. In contrary, the damaged zone in agar/agarose becomes significantly larger (> 100 times) with increasing shear modulus, which triggers the transition from formation of a small, damaged zone to activation of crack propagation. STATEMENT OF SIGNIFICANCE: We have studied cavitation nucleation and bubble growth in four different types of soft gels (i.e., tissue simulants) under translational impact. The critical linear acceleration for cavitation nucleation has been measured in the simulants by utilizing a recently developed method that mimics acceleration profiles of typical head blunt events. Each gel type exhibits significantly different trends in the critical acceleration and bubble shape (e.g., A gel-specific sphere-to-saucer transition) with increasing gel stiffness. Our theoretical framework, based on the concepts of a damaged zone and crack propagation in each gel, explains underlying mechanisms of the experimental observations. Our in-depth studies shed light on potential links between traumatic brain injuries and cavitation bubbles induced by translational acceleration, the overlooked mechanism in the literature.

Effect of random fiber networks on bubble growth in gelatin hydrogels.

In hydrodynamics, the event of dynamic bubble growth in a pure liquid under tensile pressure is known as cavitation. The same event can also be observed in soft materials (e.g., elastomers and hydrogels). However, for soft materials, bubble/cavity growth is either defined as cavitation if the bubble growth is elastic and reversible or as fracture if the cavity growth is by material failure and irreversible. In any way, bubble growth can cause damage to soft materials (e.g., tissue) by inducing high strain and strain-rate deformation. Additionally, a high-strength pressure wave is generated upon the collapse of the bubble. Therefore, it is crucial to identify the critical condition of spontaneous bubble growth in soft materials. Experimental and theoretical observations have agreed that the onset of bubble growth in soft materials requires higher tensile pressure than pure water. The extra tensile pressure is required since the cavitating bubble needs to overcome the elastic and surface energy in soft materials. In this manuscript, we developed two models to study and quantify the extra tensile pressure for different gelatin concentrations. Both the models are then compared with the existing cavitation onset criteria of rubber-like materials. Validation is done with the experimental results of threshold tensile pressure for different gelatin concentrations. Both models can moderately predict the extra tensile pressure within the intermediate range of gelatin concentrations (3-7% [w/v]). For low concentration (∼1%), the network's non-affinity plays a significant role and must be incorporated. On the other hand, for higher concentrations (∼10%), the entropic deformation dominates, and the strain energy formulation is not adequate.

An Axially Continuous Graphene-Copper Wire for High-Power Transmission: Thermoelectrical Characterization and Mechanisms.

The demand for high-power electrical transmission continues to increase with technical advances in electric vehicles, unmanned drones, portable devices, and deployable military applications. In this study, significantly enhanced electrical properties (i.e., a 450% increase in the current density breakdown limit) are demonstrated by synthesizing axially continuous graphene layers on microscale-diameter wires. To elucidate the underlying mechanisms of the observed enhancements, the electrical properties of pure copper wires and axially continuous graphene-copper (ACGC) wires with three different diameters are characterized while controlling the experimental conditions, including ambient temperature, gases, and pressure. The study reveals that the main mechanism that allows the application of extremely large current densities (>400 000 A cm-2 ) through the ACGC wires is threefold: the continuous graphene layers considerably improve: 1) surface heat dissipation (224% higher), 2) electrical conductivity (41% higher), and 3) thermal stability (41.2% lower resistivity after thermal cycles up to 450 °C), compared with pure copper wires. In addition, it is observed, through the use of high-speed camera images, that the ACGC wires exhibit very different failure behavior near the current density limit, compared with the pure copper wires.

Mechanically Induced Cavitation in Biological Systems.

Cavitation bubbles form in soft biological systems when subjected to a negative pressure above a critical threshold, and dynamically change their size and shape in a violent manner. The critical threshold and dynamic response of these bubbles are known to be sensitive to the mechanical characteristics of highly compliant biological systems. Several recent studies have demonstrated different biological implications of cavitation events in biological systems, from therapeutic drug delivery and microsurgery to blunt injury mechanisms. Due to the rapidly increasing relevance of cavitation in biological and biomedical communities, it is necessary to review the current state-of-the-art theoretical framework, experimental techniques, and research trends with an emphasis on cavitation behavior in biologically relevant systems (e.g., tissue simulant and organs). In this review, we first introduce several theoretical models that predict bubble response in different types of biological systems and discuss the use of each model with physical interpretations. Then, we review the experimental techniques that allow the characterization of cavitation in biologically relevant systems with in-depth discussions of their unique advantages and disadvantages. Finally, we highlight key biological studies and findings, through the direct use of live cells or organs, for each experimental approach.

Mechanisms of cell damage due to mechanical impact: an in vitro investigation.

The dynamic response of cells when subjected to mechanical impact has become increasingly relevant for accurate assessment of potential blunt injuries and elucidating underlying injury mechanisms. When exposed to mechanical impact, a biological system such as the human skin, brain, or liver is rapidly accelerated, which could result in blunt injuries. For this reason, an acceleration of greater than > 150 g is the most commonly used criteria for head injury. To understand the main mechanism(s) of blunt injury under such extreme dynamic threats, we have developed an innovative experimental method that applies a well-characterized and -controlled mechanical impact to live cells cultured in a custom-built in vitro setup compatible with live cell microscopy. Our studies using fibroblast cells as a model indicate that input acceleration ([Formula: see text]) alone, even when it is much greater than the typical injury criteria, e.g., [Formula: see text] g, does not result in cell damage. On the contrary, we have observed a material-dependent critical pressure value above which a sudden decrease in cell population and cell membrane damage have been observed. We have unambiguously shown that (1) this critical pressure is associated with the onset of cavitation bubbles in a cell culture chamber and (2) the dynamics of cavitation bubbles in the chamber induces localized compressive/tensile pressure cycles, with an amplitude that is considerably greater than the acceleration-induced pressure, to cells. More importantly, the rate of pressure change with time for cavitation-induced pressure is significantly faster (more than ten times) than acceleration-induced pressure. Our in vitro study on the dynamic response of biological systems due to mechanical impact is a crucial step towards understanding potential mechanism(s) of blunt injury and implementing novel therapeutic strategies post-trauma.

Problem of Diminished cRGD Surface Activity and What Can Be Done about It.

RGD peptides play a pivotal role in growing and diverse areas of biological research, ranging from in vitro experiments probing fundamental molecular mechanisms of cell adhesion to more applied in vivo strategies in medical imaging and cancer therapeutics. To better understand the outcomes of RGD-based approaches, we quantified the degree to which cyclic RGD (cRGD) activity is blocked by nonspecific binding of commonly used medium constituents. First, we show that recombinant αVß3 integrins can be used as a highly sensitive cell-free sensor to quantitatively and reliably characterize the activity of cRGD-functionalized surfaces via surface plasmon resonance (SPR). Next, SPR experiments were utilized to measure the extent of blocking of cRGD-functionalized surfaces by the commonly used agents BSA, PLL-g-PEG, and fetal calf serum (FCS)-supplemented media, using recombinant αVß3 integrin as a probe for cRGD binding activity in the presence of blocking agents. All three additives were highly efficient blockers of cRGD activity, as exemplified by cell culture media containing 1% FCS which reduced the cRGD activity by 33-fold. We then developed a strategy to combat these deleterious effects by employing the recombinant integrins as a protective cap. We show that the unblocked cRGD activity can be preserved in the presence of PLL-g-PEG by employing the αVß3 integrin as a removable protective cap, both in cell-free and in vitro experiments. In vitro studies with MDA-MB-231 cells cultured atop cRGD-functionalized surfaces found that cell adhesion and migration prevented by PLL-g-PEG were restored when this protective cap approach was used.

Prognostic Role of TMED3 in Clear Cell Renal Cell Carcinoma: A Retrospective Multi-Cohort Analysis.

Transmembrane p24 trafficking protein 3 (TMED3) is a metastatic suppressor in colon cancer and hepatocellular carcinoma. However, its function in the progression of clear cell renal cell carcinoma (ccRCC) is unknown. Here, we report that TMED3 could be a new prognostic marker for ccRCC. Patient data were extracted from cohorts in the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Differential expression of TMED3 was observed between the low stage (Stage I and II) and high stage (Stage III and IV) patients in the TCGA and ICGC cohorts and between the low grade (Grade I and II) and high grade (Grade III and IV) patients in the TCGA cohort. Further, we evaluated TMED3 expression as a prognostic gene using Kaplan-Meier survival analysis, multivariate analysis, the time-dependent area under the curve (AUC) of Uno's C-index, and the AUC of the receiver operating characteristics at 5 years. The Kaplan-Meier analysis revealed that TMED3 overexpression was associated with poor prognosis for ccRCC patients. Analysis of the C-indices and area under the receiver operating characteristic curve further supported this. Multivariate analysis confirmed the prognostic significance of TMED3 expression levels (P = 0.005 and 0.006 for TCGA and ICGC, respectively). Taken together, these findings demonstrate that TMED3 is a potential prognostic factor for ccRCC.

Acceleration-induced pressure gradients and cavitation in soft biomaterials.

The transient, dynamic response of soft materials to mechanical impact has become increasingly relevant due to the emergence of numerous biomedical applications, e.g., accurate assessment of blunt injuries to the human body. Despite these important implications, acceleration-induced pressure gradients in soft materials during impact and the corresponding material response, from small deformations to sudden bubble bursts, are not fully understood. Both through experiments and theoretical analyses, we empirically show, using collagen and agarose model systems, that the local pressure in a soft sample is proportional to the square of the sample depth in the impact direction. The critical acceleration that corresponds to bubble bursts increases with increasing gel stiffness. Bubble bursts are also highly sensitive to the initial bubble size, e.g., bubble bursts can occur only when the initial bubble diameter is smaller than a critical size (≈10 µm). Our study gives fundamental insight into the physics of injury mechanisms, from blunt trauma to cavitation-induced brain injury.

Proteomic Analysis of Hippocampus in a Mouse Model of Depression Reveals Neuroprotective Function of Ubiquitin C-terminal Hydrolase L1 (UCH-L1) via Stress-induced Cysteine Oxidative Modifications.

Chronic physical restraint stress increases oxidative stress in the brain, and dysregulation of oxidative stress can be one of the causes of major depressive disorder. To understand the underlying mechanisms, we undertook a systematic proteomic analysis of hippocampus in a chronic restraint stress mouse model of depression. Combining two-dimensional gel electrophoresis (2D-PAGE) for protein separation with nanoUPLC-ESI-q-TOF tandem mass spectrometry, we identified sixty-three protein spots that changed in the hippocampus of mice subjected to chronic restraint stress. We identified and classified the proteins that changed after chronic stress, into three groups respectively functioning in neural plasticity, metabolic processes and protein aggregation. Of these, 5 proteins including ubiquitin C-terminal hydrolase L1 (UCH-L1), dihydropyrimidinase-related protein 2 (DPYL2), haloacid dehalogenase-like hydrolase domain-containing protein 2 (HDHD2), actin-related protein 2/3 complex subunit 5 (ARPC5) and peroxiredoxin-2 (PRDX2), showed pI shifts attributable to post-translational modifications. Further analysis indicated that UCH-L1 underwent differential oxidations of 2 cysteine residues following chronic stress. We investigated whether the oxidized form of UCH-L1 plays a role in stressed hippocampus, by comparing the effects of UCH-L1 and its Cys mutants on hippocampal cell line HT-22 in response to oxidative stress. This study demonstrated that UCH-L1 wild-type and cysteine to aspartic acid mutants, but not its cysteine to serine mutants, afforded neuroprotective effects against oxidative stress; there were no discernible differences between wild-type UCH-L1 and its mutants in the absence of oxidative stress. These findings suggest that cysteine oxidative modifications of UCH-L1 in the hippocampus play key roles in neuroprotection against oxidative stress caused in major depressive disorder.

Cavitation nucleation in gelatin: Experiment and mechanism.

Dynamic cavitation in soft materials is becoming increasingly relevant due to emerging medical implications such as the potential of cavitation-induced brain injury or cavitation created by therapeutic medical devices. However, the current understanding of dynamic cavitation in soft materials is still very limited, mainly due to lack of robust experimental techniques. To experimentally characterize cavitation nucleation under dynamic loading, we utilize a recently developed experimental instrument, the integrated drop tower system. This technique allows quantitative measurements of the critical acceleration (acr) that corresponds to cavitation nucleation while concurrently visualizing time evolution of cavitation. Our experimental results reveal that acr increases with increasing concentration of gelatin in pure water. Interestingly, we have observed the distinctive transition from a sharp increase (pure water to 1% gelatin) to a much slower rate of increase (∼10× slower) between 1% and 7.5% gelatin. Theoretical cavitation criterion predicts the general trend of increasing acr, but fails to explain the transition rates. As a likely mechanism, we consider concentration-dependent material properties and non-spherical cavitation nucleation sites, represented by pre-existing bubbles in gels, due to possible interplay between gelatin molecules and nucleation sites. This analysis shows that cavitation nucleation is very sensitive to the initial configuration of a bubble, i.e., a non-spherical bubble can significantly increase acr. This conclusion matches well with the experimentally observed liquid-to-gel transition in the critical acceleration for cavitation nucleation. STATEMENT OF SIGNIFICANCE: From a medical standpoint, understanding dynamic cavitation within soft materials, i.e., tissues, is important as there are both potential injury implications (blast-induced cavitation within the brain) as well as treatments utilizing the phenomena (lithotripsy). In this regard, the main results of the present work are (1) quantitative characterization of cavitation nucleation in gelatin samples as a function of gel concentration utilizing well-controlled mechanical impacts and (2) mechanistic understanding of complex coupling between cavitation and liquid-/solid-like material properties of gel. The new capabilities of testing soft gels, which can be tuned to mimic material properties of target organs, at high loading rate conditions and accurately predicting their cavitation behavior are an important step towards developing reliable cavitation criteria in the scope of their biomedical applications.

Heterogeneous nuclear ribonucleoprotein K inhibits heat shock-induced transcriptional activity of heat shock factor 1.

When cells are exposed to heat shock and various other stresses, heat shock factor 1 (HSF1) is activated, and the heat shock response (HSR) is elicited. To better understand the molecular regulation of the HSR, we used 2D-PAGE-based proteome analysis to screen for heat shock-induced post-translationally modified cellular proteins. Our analysis revealed that two protein spots typically present on 2D-PAGE gels and containing heterogeneous nuclear ribonucleoprotein K (hnRNP K) with trioxidized Cys132 disappeared after the heat shock treatment and reappeared during recovery, but the total amount of hnRNP K protein remained unchanged. We next tested whether hnRNP K plays a role in HSR by regulating HSF1 and found that hnRNP K inhibits HSF1 activity, resulting in reduced expression of hsp70 and hsp27 mRNAs. hnRNP K also reduced binding affinity of HSF1 to the heat shock element by directly interacting with HSF1 but did not affect HSF1 phosphorylation-dependent activation or nuclear localization. hnRNP K lost its ability to induce these effects when its Cys132 was substituted with Ser, Asp, or Glu. These findings suggest that hnRNP K inhibits transcriptional activity of HSF1 by inhibiting its binding to heat shock element and that the oxidation status of Cys132 in hnRNP K is critical for this inhibition.

A Novel Method for In Situ Electromechanical Characterization of Nanoscale Specimens.

Electrically assisted deformation (EAD) is increasingly being used to improve the formability of metals during processes such as sheet metal rolling and forging. Adoption of this technique is proceeding despite disagreement concerning the underlying mechanism responsible for EAD. The experimental procedure described herein enables a more explicit study compared to previous EAD research by removing thermal effects, which are responsible for disagreement in interpreting previous EAD results. Furthermore, as the procedure described here enables EAD observation in situ and in real time in a transmission electron microscope (TEM), it is superior to existing post-mortem methods that observe EAD effects post-test. Test samples consist of a single crystal copper (SCC) foil having a free-standing tensile test section of nanoscale thickness, fabricated using a combination of laser and ion beam milling. The SCC is mounted to an etched silicon base that provides mechanical support and electrical isolation while serving as a heat sink. Using this geometry, even at high current density (~3,500 A/mm2), the test section experiences a negligible temperature increase (<0.02 °C), thus eliminating Joule heating effects. Monitoring material deformation and identifying the corresponding changes to microstructures, e.g. dislocations, are accomplished by acquiring and analyzing a series of TEM images. Our sample preparation and in situ experiment procedures are robust and versatile as they can be readily utilized to test materials with different microstructures, e.g., single and polycrystalline copper.

Characterization and detection of acceleration-induced cavitation in soft materials using a drop-tower-based integrated system.

The material response of biologically relevant soft materials, e.g., extracellular matrix or cell cytoplasm, at high rate loading conditions is becoming increasingly important for emerging medical implications including the potential of cavitation-induced brain injury or cavitation created by medical devices, whether intentional or not. However, accurately probing soft samples remains challenging due to their delicate nature, which often excludes the use of conventional techniques requiring direct contact with a sample-loading frame. We present a drop-tower-based method, integrated with a unique sample holder and a series of effective springs and dampers, for testing soft samples with an emphasis on high-rate loading conditions. Our theoretical studies on the transient dynamics of the system show that well-controlled impacts between a movable mass and sample holder can be used as a means to rapidly load soft samples. For demonstrating the integrated system, we experimentally quantify the critical acceleration that corresponds to the onset of cavitation nucleation for pure water and 7.5% gelatin samples. This study reveals that 7.5% gelatin has a significantly higher, approximately double, critical acceleration as compared to pure water. Finally, we have also demonstrated a non-optical method of detecting cavitation in soft materials by correlating cavitation collapse with structural resonance of the sample container.

In situ thermomechanical testing methods for micro/nano-scale materials.

The advance of micro/nanotechnology in energy-harvesting, micropower, electronic devices, and transducers for automobile and aerospace applications has led to the need for accurate thermomechanical characterization of micro/nano-scale materials to ensure their reliability and performance. This persistent need has driven various efforts to develop innovative experimental techniques that overcome the critical challenges associated with precise mechanical and thermal control of micro/nano-scale specimens during material characterization. Here we review recent progress in the development of thermomechanical testing methods from miniaturized versions of conventional macroscopic test systems to the current state of the art of in situ uniaxial testing capabilities in electron microscopes utilizing either indentation-based microcompression or integrated microsystems. We discuss the major advantages/disadvantages of these methods with respect to specimen size, range of temperature control, ease of experimentation and resolution of the measurements. We also identify key challenges in each method. Finally, we summarize some of the important discoveries that have been made using in situ thermomechanical testing and the exciting research opportunities still to come in micro/nano-scale materials.

In situ electron microscopy studies of electromechanical behavior in metals at the nanoscale using a novel microdevice-based system.

Electrically assisted deformation (EAD) is an emerging technique to enhance formability of metals by applying an electric current through them. Despite its increasing importance in manufacturing applications, there is still an unresolved debate on the nature of the fundamental deformation mechanisms underlying EAD, mainly between electroplasticity (non-thermal effects) and resistive heating (thermal effects). This status is due to two critical challenges: (1) a lack of experimental techniques to directly observe fundamental mechanisms of material deformation during EAD, and (2) intrinsic coupling between electric current and Joule heating giving rise to unwanted thermally activated mechanisms. To overcome these challenges, we have developed a microdevice-based electromechanical testing system (MEMTS) to characterize nanoscale metal specimens in transmission electron microscopy (TEM). Our studies reveal that MEMTS eliminates the effect of Joule heating on material deformation, a critical advantage over macroscopic experiments, owing to its unique scale. For example, a negligible change in temperature (<0.02 °C) is predicted at ∼3500 A/mm2. Utilizing the attractive features of MEMTS, we have directly investigated potential electron-dislocation interactions in single crystal copper (SCC) specimens that are simultaneously subjected to uniaxial loading and electric current density up to 5000 A/mm2. Our in situ TEM studies indicate that for SCC, electroplasticity does not play a key role as no differences in dislocation activities, such as depinning and movement, are observed.

Micro- and Nanoscale Technologies for Delivery into Adherent Cells.

Several recent micro- and nanotechnologies have provided novel methods for biological studies of adherent cells because the small features of these new biotools provide unique capabilities for accessing cells without the need for suspension or lysis. These novel approaches have enabled gentle but effective delivery of molecules into specific adhered target cells, with unprecedented spatial resolution. We review here recent progress in the development of these technologies with an emphasis on in vitro delivery into adherent cells utilizing mechanical penetration or electroporation. We discuss the major advantages and limitations of these approaches and propose possible strategies for improvements. Finally, we discuss the impact of these technologies on biological research concerning cell-specific temporal studies, for example non-destructive sampling and analysis of intracellular molecules.