From the Cover: Materials and noncoplanar mesh designs for integrated circuits with linear elastic responses to extreme mechanical deformations

Electronic systems that offer elastic mechanical responses to high-strain deformations are of growing interest because of their ability to enable new biomedical devices and other applications whose requirements are impossible to satisfy with conventional wafer-based technologies or even with those that offer simple bendability. This article introduces materials and mechanical design strategies for classes of electronic circuits that offer extremely high stretchability, enabling them to accommodate even demanding configurations such as corkscrew twists with tight pitch (e.g., 90° in ≈1 cm) and linear stretching to “rubber-band” levels of strain (e.g., up to ≈140%). The use of single crystalline silicon nanomaterials for the semiconductor provides performance in stretchable complementary metal-oxide-semiconductor (CMOS) integrated circuits approaching that of conventional devices with comparable feature sizes formed on silicon wafers. Comprehensive theoretical studies of the mechanics reveal the way in which the structural designs enable these extreme mechanical properties without fracturing the intrinsically brittle active materials or even inducing significant changes in their electrical properties. The results, as demonstrated through electrical measurements of arrays of transistors, CMOS inverters, ring oscillators, and differential amplifiers, suggest a valuable route to high-performance stretchable electronics.     

From the Cover: Wireless power transfer to deep-tissue microimplants

The ability to implant electronic systems in the human body has led to many medical advances. Progress in semiconductor technology paved the way for devices at the scale of a millimeter or less (“microimplants”), but the miniaturization of the power source remains challenging. Although wireless powering has been demonstrated, energy transfer beyond superficial depths in tissue has so far been limited by large coils (at least a centimeter in diameter) unsuitable for a microimplant. Here, we show that this limitation can be overcome by a method, termed midfield powering, to create a high-energy density region deep in tissue inside of which the power-harvesting structure can be made extremely small. Unlike conventional near-field (inductively coupled) coils, for which coupling is limited by exponential field decay, a patterned metal plate is used to induce spatially confined and adaptive energy transport through propagating modes in tissue. We use this method to power a microimplant (2 mm, 70 mg) capable of closed-chest wireless control of the heart that is orders of magnitude smaller than conventional pacemakers. With exposure levels below human safety thresholds, milliwatt levels of power can be transferred to a deep-tissue (>5 cm) microimplant for both complex electronic function and physiological stimulation. The approach developed here should enable new generations of implantable systems that can be integrated into the body at minimal cost and risk.Progress in semiconductor technology has led to electronic devices that can augment or replace physiological functions; their ability to be implanted for direct interaction with organ systems relies on overall miniaturization of the device for simplified delivery (e.g., via catheter or hypodermic needle) and access to interstitial spaces. Advances over the past few decades enable most components in a biomedical device, including electrodes, oscillators, memory, and wireless communication systems, to be integrated on tiny silicon chips. However, the energy required for electronic function remains substantial and the consumption density has not been matched by existing powering technologies (1). As a result, the vast bulk of most implantable electronic devices consists of energy storage or harvesting components.Although considerable progress has been made in energy storage technologies, batteries remain a major obstacle to miniaturization (2, 3) because their lifetimes are limited and highly constrained by the available volume, requiring periodic surgical replacement once the unit is depleted. Energy-harvesting strategies have been developed to eliminate batteries or to extend their function. Previous demonstrations include thermoelectric (4), piezoelectric (5–7), biopotential (8), or glucose (9, 10) power extraction. However, these methods are anatomically specific and, in their existing forms, yield power densities too low (<0.1 μW/mm²) for a microimplant.Alternatively, energy can be transferred from an external source. Ideally, power transfer should be completely noninvasive and not specific to regions in the body. Most existing approaches for this type of transfer are based on electromagnetic coupling in the near field (11–20). Though well-suited for large devices and prostheses (21, 22), near-field methods do not address key challenges to powering a microimplant: weak coupling between extremely asymmetric source and receiver structures (23), dissipative and heterogeneous tissue (24), and regulatory power thresholds for general safety (25). These challenges, compounded by the intrinsic exponential decay of the near field, severely limit miniaturization beyond superficial depths (>1 cm), even if the battery can be removed.Theory has indicated that these problems can be overcome in the electromagnetic midfield (23): energy transfer in this region, defined to be about a wavelength’s distance from the source, occurs through the coupling between evanescent fields in air and propagating modes in tissue. Using a patterned metal plate to control the near field, we demonstrate milliwatt levels of power transfer to a miniaturized coil deep in heterogeneous tissue (>5 cm), with exposure levels below safety thresholds for humans; this enables us to power a microimplant capable of delivering controlled electrical pulses to nearly anywhere in the body. The device consists of a multiturn coil structure, rectifying circuits for AC/DC power conversion, a silicon-on-insulator integrated circuit (IC) for pulse control, and electrodes, entirely assembled within a 2-mm diameter, 3.5-mm height device small enough to fit inside a catheter. We demonstrate wireless function by operating it in human-scale heart and brain environments, and by wirelessly regulating cardiac rhythm through a chest wall.     

From the Cover: Patterning droplets with durotaxis

Numerous cell types have shown a remarkable ability to detect and move along gradients in stiffness of an underlying substrate—a process known as durotaxis. The mechanisms underlying durotaxis are still unresolved, but generally believed to involve active sensing and locomotion. Here, we show that simple liquid droplets also undergo durotaxis. By modulating substrate stiffness, we obtain fine control of droplet position on soft, flat substrates. Unlike other control mechanisms, droplet durotaxis works without imposing chemical, thermal, electrical, or topographical gradients. We show that droplet durotaxis can be used to create large-scale droplet patterns and is potentially useful for many applications, such as microfluidics, thermal control, and microfabrication.     

From the Cover: Ancient origin of the integrin-mediated adhesion and signaling machinery

The evolution of animals (metazoans) from their unicellular ancestors required the emergence of novel mechanisms for cell adhesion and cell–cell communication. One of the most important cell adhesion mechanisms for metazoan development is integrin-mediated adhesion and signaling. The integrin adhesion complex mediates critical interactions between cells and the extracellular matrix, modulating several aspects of cell physiology. To date this machinery has been considered strictly metazoan specific. Here we report the results of a comparative genomic analysis of the integrin adhesion machinery, using genomic data from several unicellular relatives of Metazoa and Fungi. Unexpectedly, we found that core components of the integrin adhesion complex are encoded in the genome of the apusozoan protist Amastigomonas sp., and therefore their origins predate the divergence of Opisthokonta, the clade that includes metazoans and fungi. Furthermore, our analyses suggest that key components of this apparatus have been lost independently in fungi and choanoflagellates. Our data highlight the fact that many of the key genes that had formerly been cited as crucial for metazoan origins have a much earlier origin. This underscores the importance of gene cooption in the unicellular-to-multicellular transition that led to the emergence of the Metazoa.     

From the Cover: N-cadherin-dependent neuron–neuron interaction is required for the maintenance of activity-induced dendrite growth

Formation of neural circuits depends on stable contacts between neuronal processes, mediated by interaction of cell adhesion molecules, including N-cadherin. In the present study, we found that activity-dependent dendrite arborization specifically requires N-cadherin–mediated extracellular neuron–neuron interaction, because the enhancement did not occur for neurons cultured in isolation or plated on an astrocyte monolayer and was abolished by a recombinant soluble N-cadherin ectodomain. Furthermore, depolarization elevated the level of membrane-associated cadherin/catenin complexes and surface N-cadherin. Importantly, surface N-cadherin elevation is specifically required for the maintenance of nascent dendrite arbors. Through loss- and gain-of-function approaches, we showed that N-cadherin-mediated dendrite growth requires association of the cadherin/catenin complex with the actin cytoskeleton. In summary, these results identify a previously unexplored and specific function for activity-induced, N-cadherin–mediated neuron–neuron contacts in the maintenance of dendrite arbors.     

From the Cover: Evening use of light-emitting eReaders negatively affects sleep,circadian timing,and next-morning alertness

In the past 50 y, there has been a decline in average sleep duration and quality, with adverse consequences on general health. A representative survey of 1,508 American adults recently revealed that 90% of Americans used some type of electronics at least a few nights per week within 1 h before bedtime. Mounting evidence from countries around the world shows the negative impact of such technology use on sleep. This negative impact on sleep may be due to the short-wavelength–enriched light emitted by these electronic devices, given that artificial-light exposure has been shown experimentally to produce alerting effects, suppress melatonin, and phase-shift the biological clock. A few reports have shown that these devices suppress melatonin levels, but little is known about the effects on circadian phase or the following sleep episode, exposing a substantial gap in our knowledge of how this increasingly popular technology affects sleep. Here we compare the biological effects of reading an electronic book on a light-emitting device (LE-eBook) with reading a printed book in the hours before bedtime. Participants reading an LE-eBook took longer to fall asleep and had reduced evening sleepiness, reduced melatonin secretion, later timing of their circadian clock, and reduced next-morning alertness than when reading a printed book. These results demonstrate that evening exposure to an LE-eBook phase-delays the circadian clock, acutely suppresses melatonin, and has important implications for understanding the impact of such technologies on sleep, performance, health, and safety.The use of electronic devices for reading, communication, and entertainment has greatly increased in recent years. Greater portability, convenience, and ease of access to reading materials in electronic form add to the popularity of these devices. The use of light-emitting devices immediately before bedtime is a concern because light is the most potent environmental signal that impacts the human circadian clock and may therefore play a role in perpetuating sleep deficiency (1). The circadian-timing system synchronizes numerous internal physiological and biochemical processes, including the daily rhythm of sleep propensity (2), to external environmental time cues. For optimal sleep duration and quality, the timing of the sleep episode must be appropriately aligned with the timing of the circadian clock. In humans, exposure to light in the evening and early part of the night, even at low intensity, suppresses the release of the sleep-facilitating hormone melatonin (3–5) and shifts the circadian clock to a later time (3, 6), both of which make it more difficult to fall asleep at night. Light exposure in the biological evening/night also acutely increases alertness (7, 8), but not much is known about its impact on alertness the following day. Here we present results from a randomized study comparing the effects of reading before bedtime using a light-emitting eReader (LE-eBook) with reading a printed book by reflected light. We examined circadian timing and suppression of melatonin, polysomnographic (PSG) recordings of sleep, and subjective and objective measures of sleepiness both in the evening while reading and the following morning.     

From the Cover: Discovery of a cardiolipin synthase utilizing phosphatidylethanolamine and phosphatidylglycerol as substrates

Depending on growth phase and culture conditions, cardiolipin (CL) makes up 5–15% of the phospholipids in Escherichia coli with the remainder being primarily phosphatidylethanolamine (PE) and phosphatidylglycerol (PG). In E. coli, the cls and ybhO genes (renamed clsA and clsB, respectively) each encode a CL synthase (Cls) that catalyzes the condensation of two PG molecules to form CL and glycerol. However, a ∆clsAB mutant still makes CL in the stationary phase, indicating the existence of additional Cls. We identified a third Cls encoded by ymdC (renamed clsC). ClsC has sequence homology with ClsA and ClsB, which all belong to the phospholipase D superfamily. The ∆clsABC mutant lacks detectible CL regardless of growth phase or growth conditions. CL can be restored to near wild-type levels in stationary phase in the triple mutant by expressing either clsA or clsB. Expression of clsC alone resulted in a low level of CL in the stationary phase, which increased to near wild-type levels by coexpression of its neighboring gene, ymdB. CL synthesis by all Cls is increased with increasing medium osmolarity during logarithmic growth and in stationary phase. However, only ClsA contributes detectible levels of CL at low osmolarity during logarithmic growth. Mutation of the putative catalytic motif of ClsC prevents CL formation. Unlike eukaryotic Cls (that use PG and CDP-diacylglycerol as substrates) or ClsA, the combined YmdB-ClsC used PE as the phosphatidyl donor to PG to form CL, which demonstrates a third and unique mode for CL synthesis.     

From the Cover: Carnivorous leaves from Baltic amber

The fossil record of carnivorous plants is very scarce and macrofossil evidence has been restricted to seeds of the extant aquatic genus Aldrovanda of the Droseraceae family. No case of carnivorous plant traps has so far been reported from the fossil record. Here, we present two angiosperm leaves enclosed in a piece of Eocene Baltic amber that share relevant morphological features with extant Roridulaceae, a carnivorous plant family that is today endemic to the Cape flora of South Africa. Modern Roridula species are unique among carnivorous plants as they digest prey in a complex mutualistic association in which the prey-derived nutrient uptake depends on heteropteran insects. As in extant Roridula, the fossil leaves possess two types of plant trichomes, including unicellular hairs and five size classes of multicellular stalked glands (or tentacles) with an apical pore. The apices of the narrow and perfectly tapered fossil leaves end in a single tentacle, as in both modern Roridula species. The glandular hairs of the fossils are restricted to the leaf margins and to the abaxial lamina, as in extant Roridula gorgonias. Our discovery supports current molecular age estimates for Roridulaceae and suggests a wide Eocene distribution of roridulid plants.Plant carnivory is traditionally defined as the attraction, capture, and digestion of prey by vegetative traps, with the subsequent uptake of nutrients (1, 2). Some carnivorous plants, however, challenge the boundary of the botanical carnivory concept because they depend on commensal organisms for the digestion of their prey (2, 3). The most famous representative of those plants is Roridula, placed in the monogeneric family Roridulaceae that is endemic to a few localities in the southwestern Cape of South Africa (4, 5).The resinous glandular leaves of both extant species, Roridula dentata and Roridula gorgonias, capture plenty of arthropods. The sticky trapping glue of Roridula is a viscous lipophilic resin containing triterpenoids as major component, which does not allow dissolution of digestive enzymes (6). Consequently, the secretory glands of Roridulaceae lack enzymatic activity (7, 8). For prey-derived nutrient uptake, Roridula depends on two obligately associated heteropteran Pameridea species (family Miridae, “capsid bugs”), which feed on the trapped animals (5, 9). In this “digestive mutualism” (10), the nutrient-rich fecal compounds of these “Roridula bugs” are incorporated by Roridula through nanometer-sized cuticular gaps and serve for a better alimentation in a nutrient-poor habitat (7, 8, 10, 11). The benefit of nutrient uptake from captured prey is the essential criterion for the concept of botanical carnivory (1, 2) and thus includes Roridulaceae (11, 12).Here, we report two leaf fossils from Eocene Baltic amber possessing the relevant morphological features of an adhesive flypaper trap plant that we assign to the Roridulaceae lineage (Figs. 1–3). Both specimens originate from the Jantarny amber mine near Kaliningrad (Russia). The amber-bearing sediments of this fossil site date to 35–47 million years ago (13, 14).Open in a separate windowFig. 1.Carnivorous leaves from Eocene Baltic amber. (A) Overview of the leaf enclosed in amber specimen GZG.BST.27310 showing the adaxial tentacle-free side in slightly oblique view and stalked glands at the margin and on the abaxial side; arrowhead points to the exceptional long tentacle stalk with several branched oak trichomes attached. (B) Overview of the leaf enclosed in amber specimen GZG.BST.27311, showing abundant tentacles on the abaxial side. (C) Margin of abaxial leaf surface with tentacles of different size classes and nonglandular hyaline trichomes. (D) Leaf apex tapering into a sole tentacle. (E and F) Glandular heads with central pore (arrowheads) from both leaves. (Scale bars: A and B, 1 mm; C and D, 100 µm; E, 10 μm; F, 40 μm.)Open in a separate windowFig. 3.Carnivorous leaf from Eocene Baltic amber (A and B; GZG.BST.27310) and leaves of extant Roridula gorgonias (C and D). (A) Exceptionally long tentacle stalk (with several branched oak trichomes attached) of the fossil leaf representing the fifth size class of stalked glands. (B and C) Overviews showing the tentacle-free adaxial surface and tentacles along the leaf margins. (D) Partial leaf tip showing different size classes of stalked glands. (Scale bars: A, 100 µm; B, 500 µm; C and D, 1 mm.)     

From the Cover: The mechanics of slithering locomotion

In this experimental and theoretical study, we investigate the slithering of snakes on flat surfaces. Previous studies of slithering have rested on the assumption that snakes slither by pushing laterally against rocks and branches. In this study, we develop a theoretical model for slithering locomotion by observing snake motion kinematics and experimentally measuring the friction coefficients of snakeskin. Our predictions of body speed show good agreement with observations, demonstrating that snake propulsion on flat ground, and possibly in general, relies critically on the frictional anisotropy of their scales. We have also highlighted the importance of weight distribution in lateral undulation, previously difficult to visualize and hence assumed uniform. The ability to redistribute weight, clearly of importance when appendages are airborne in limbed locomotion, has a much broader generality, as shown by its role in improving limbless locomotion.     

From the Cover: The emergence of lineage-specific chromosomal topologies from coordinate gene regulation

Although the importance of chromosome organization during mitosis is clear, it remains to be determined whether the nucleus assumes other functionally relevant chromosomal topologies. We have previously shown that homologous chromosomes have a tendency to associate during hematopoiesis according to their distribution of coregulated genes, suggesting cell-specific nuclear organization. Here, using the mathematical approaches of distance matrices and coupled oscillators, we model the dynamic relationship between gene expression and chromosomal associations during the differentiation of a multipotential hematopoietic progenitor. Our analysis reveals dramatic changes in total genomic order: Commitment of the progenitor results in an initial increase in entropy at both the level of gene coregulation and chromosomal organization, which we suggest represents a phase transition, followed by a progressive decline in entropy during differentiation. The stabilization of a highly ordered state in the differentiated cell types results in lineage-specific chromosomal topologies and is related to the emergence of coherence—or self-organization—between chromosomal associations and coordinate gene regulation. We discuss how these observations may be generally relevant to cell fate decisions encountered by progenitor/stem cells.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:From the Cover: Atomic-scale insight and design principles for turbine engine thermal barrier coatings from theory

To maximize energy efficiency, gas turbine engines used in airplanes and for power generation operate at very high temperatures, even above the melting point of the metal alloys from which they are comprised. This feat is accomplished in part via the deposition of a multilayer, multicomponent thermal barrier coating (TBC), which lasts up to approximately 40,000 h before failing. Understanding failure mechanisms can aid in designing circumvention strategies. We review results of quantum mechanics calculations used to test hypotheses about impurities that harm TBCs and transition metal (TM) additives that render TBCs more robust. In particular, we discovered a number of roles that Pt and early TMs such as Hf and Y additives play in extending the lifetime of TBCs. Fundamental insight into the nature of the bonding created by such additives and its effect on high-temperature evolution of the TBCs led to design principles that can be used to create materials for even more efficient engines.     

From the Cover: Regulation of cell motile behavior by crosstalk between cadherin- and integrin-mediated adhesions

During normal development and in disease, cohesive tissues undergo rearrangements that require integration of signals from cell adhesions to neighboring cells and to the extracellular matrix (ECM). How a range of cell behaviors is coordinated by these different adhesion complexes is unknown. To analyze epithelial cell motile behavior in response to combinations of cell–ECM and cell–cell adhesion cues, we took a reductionist approach at the single-cell scale by using unique, functionalized micropatterned surfaces comprising alternating stripes of ECM (collagenIV) and adjustable amounts of E-cadherin-Fc (EcadFc). On these surfaces, individual cells spatially segregated integrin- and cadherin-based complexes between collagenIV and EcadFc surfaces, respectively. Cell migration required collagenIV and did not occur on surfaces functionalized with only EcadFc. However, E-cadherin adhesion dampened lamellipodia activity on both collagenIV and EcadFc surfaces and biased the direction of cell migration without affecting the migration rate, all in an EcadFc concentration-dependent manner. Traction force microscopy showed that spatial confinement of integrin-based adhesions to collagenIV stripes induced anisotropic cell traction on collagenIV and migration directional bias. Selective depletion of different pools of αE-catenin, an E-cadherin and actin binding protein, identified a membrane-associated pool required for E-cadherin–mediated adhesion and down-regulation of lamellipodia activity and a cytosolic pool that down-regulated the migration rate in an E-cadherin adhesion-independent manner. These results demonstrate that there is crosstalk between E-cadherin– and integrin-based adhesion complexes and that E-cadherin regulates lamellipodia activity and cell migration directionality, but not cell migration rate.     

From the Cover: The skeleton of tropical intraseasonal oscillations

The Madden–Julian oscillation (MJO) is the dominant mode of variability in the tropical atmosphere on intraseasonal timescales and planetary spatial scales. Despite the primary importance of the MJO and the decades of research progress since its original discovery, a generally accepted theory for its essential mechanisms has remained elusive. Here, we present a minimal dynamical model for the MJO that recovers robustly its fundamental features (i.e., its “skeleton”) on intraseasonal/planetary scales: (i) the peculiar dispersion relation of dω/dk ≈ 0, (ii) the slow phase speed of ≈5 m/s, and (iii) the horizontal quadrupole vortex structure. This is accomplished here in a model that is neutrally stable on planetary scales; i.e., it is tacitly assumed that the primary instabilities occur on synoptic scales. The key premise of the model is that modulations of synoptic scale wave activity are induced by low-level moisture preconditioning on planetary scales, and they drive the “skeleton” of the MJO through modulated heating. The “muscle” of the MJO—including tilts, vertical structure, etc.—is contributed by other potential upscale transport effects from the synoptic scales.     

From the Cover: Enabling enhanced emission and low-threshold lasing of organic molecules using special Fano resonances of macroscopic photonic crystals

The nature of light interaction with matter can be dramatically altered in optical cavities, often inducing nonclassical behavior. In solid-state systems, excitons need to be spatially incorporated within nanostructured cavities to achieve such behavior. Although fascinating phenomena have been observed with inorganic nanostructures, the incorporation of organic molecules into the typically inorganic cavity is more challenging. Here, we present a unique optofluidic platform comprising organic molecules in solution suspended on a photonic crystal surface, which supports macroscopic Fano resonances and allows strong and tunable interactions with the molecules anywhere along the surface. We develop a theoretical framework of this system and present a rigorous comparison with experimental measurements, showing dramatic spectral and angular enhancement of emission. We then demonstrate that these enhancement mechanisms enable lasing of only a 100-nm thin layer of diluted solution of organic molecules with substantially reduced threshold intensity, which has important implications for organic light-emitting devices and molecular sensing.