As the chair of Duke University’s Department of Biomedical Engineering (BME), I am pleased to present this comprehensive Nature Reprint Collection, which showcases the breadth of innovative scholarship in the department over the past decade.
Department of Biomedical Engineering at Duke University
One of the first biomedical engineering programs in the United States, the Department of Biomedical Engineering at Duke University consistently ranks among the best in the world. As the department has grown, our faculty have continued to pioneer new areas of biomedical engineering, with strengths in tissue engineering, biomaterials, drug delivery, biophotonics and neuroengineering. Duke BME’s ethos reflects the department’s aspiration to advance biomedical engineering to serve society. As we strive towards this goal, we continue to attract outstanding faculty and students who create innovative solutions to the world’s most challenging healthcare problems.
This collection of articles from Nature Research journals is produced with support from Duke University. Duke University retains sole responsibility for the selection of articles.
Established in 1967 by Duke University’s schools of medicine and engineering, the Duke Department of Biomedical Engineering (BME) was one of the first of its kind in the United States and consistently ranks among the best in the world.
Genetically encoded lipid–polypeptide hybrid biomaterials that exhibit temperature-triggered hierarchical self-assembly
Inspired by the post-translational modifications of polypeptides widespread in biological systems, the one-pot synthesis of biohybrid materials was engineered within Escherichia coli using a recombinant expression and post-translational lipidation. The fatty-acid-modified elastin-like polypeptides (FAMEs) prepared, which comprise peptide-amphiphile segments prone to self-assembly fused to a thermally responsive elastin-like polypeptide, exhibit temperature-triggered hierarchical assembly.
The generation of functional skeletal muscle tissue from human pluripotent stem cells has not been reported. Here, the authors describe engineering of contractile skeletal muscle bundles in culture, which become vascularized and maintain functionality when transplanted into mice.
It is unclear whether the transfer of plasmids carrying antibiotic resistance genes can explain their persistence when antibiotics are not present. Here, Lopatkin et al. show that conjugal plasmids, even when costly, are indeed transferred at sufficiently high rates to be maintained in the absence of antibiotics.
Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues
Cardiomyocytes derived from human induced pluripotent stem cells could be used to generate cardiac tissues for regenerative purposes. Here the authors describe a method to obtain large bioengineered heart tissues showing advanced maturation, functional features and engraftment capacity.
Engineered bacteria self-assemble to generate structures that act as pressure sensors.
Group 2 innate lymphoid cells (ILC2s) are entangled with cholinergic SNAP-25-expressing neurons. David Artis and colleagues report that ILC2s express the neuropeptide receptor NMUR1, making them responsive to neuronal neuromedin. In mice, this promoted a tissue-protective type 2 response and accelerated expulsion of the gastrointestinal nematode Nippostrongylus brasiliensis. Elsewhere in this issue, Henrique Veiga-Fernandes and colleagues also provide evidence that ILC2s express Nmur1 and respond to neuromedin expressed by adjacent enteric neurons. In mice, the interaction results in an enhanced and immediate response of ILC2s to infection by the parasite N. brasiliensis.
The neonatal mouse heart can regenerate during a limited time period after birth, but this property is rapidly lost. Eldad Tzahor and colleagues identify a component of the neonatal heart extracellular matrix, agrin, which is required for heart regeneration in neonatal mice. They further show that recombinant agrin can be used to improve the function of adult mouse hearts after myocardial infarction. The mechanism by which agrin can promote heart function and regeneration may be multi-faceted, but the authors also show that it can boost cardiomyocyte proliferation, which could contribute to the observed effects.
Generation and comparison of CRISPR-Cas9 and Cre-mediated genetically engineered mouse models of sarcoma
Site-specific recombination and CRISPR-Cas9 have been used to generate genetically engineered mouse models of cancer. Here the authors compare sarcomas generated using both systems and see similar genetic and cellular phenotypes, suggesting CRISPR-Cas9 can be used to rapidly generate sarcoma models.
One-week glucose control via zero-order release kinetics from an injectable depot of glucagon-like peptide-1 fused to a thermosensitive biopolymer
An optimized formulation of glucagon-like peptide-1 recombinantly fused to an elastin-like polypeptide leads to zero-order release kinetics from a subcutaneous depot and to 10 days of glycaemic control in three mouse models of diabetes.
CRISPR–Cas9 epigenome editing enables high-throughput screening for functional regulatory elements in the human genome
Regulatory elements for specific human genes are rapidly identified with CRISPR epigenome editing.
Programming molecular self-assembly of intrinsically disordered proteins containing sequences of low complexity
A programmable model of membraneless organelles comprised of intrinsically disordered proteins (IDPs) containing sequences of low complexity has now been developed. The rules governing the assembly of archetypal IDPs into biologically inspired mixed, layered and size-controlled configurations provides a new means for understanding intracellular phase behaviour of IDPs.
Capacitively coupled arrays of multiplexed flexible silicon transistors for long-term cardiac electrophysiology
Capacitive coupling between tissue and flexible integrated electronics through a sealing dielectric layer facilitates long-term electrophysiology measurements, as demonstrated in ex vivo Langendorff heart models.
A brush-polymer/exendin-4 conjugate reduces blood glucose levels for up to five days and eliminates poly(ethylene glycol) antigenicity
Conjugation of exendin-4 — a drug to treat type 2 diabetes — with a poly(ethylene glycol) (PEG)-based brush polymer reduces the conjugate's reactivity towards anti-PEG antibodies and leads to lower blood glucose levels in mice for up to 5 days after a single injection.
Restoring lost excitability of injured tissue is a paramount of regenerative medicine. By using a combined expression of bacterial voltage-gated Na+ channel, Kir2.1, and connexin-43 in non-excitable human fibroblasts, here the authors generate excitable cells that rescue action potential conduction in an in vitromodel of cardiac fibrosis.
In vivo cellular-resolution retinal imaging in infants and children using an ultracompact handheld probe
A handheld probe enables retinal imaging in children.
Bioresorbable silicon electronics for transient spatiotemporal mapping of electrical activity from the cerebral cortex
Arrays of bioresorbable, highly doped silicon electrodes with multiplexing capabilities are used as electrocorticography sensors to perform in vivo, reliable acute and chronic recordings for up to one month before dissolving in the body.
Antibiotic-mediated selection may promote or suppress conjugation dynamics, dependent on the population structure, physiological status of cells and energy availability.
Combinatorial codon scrambling enables scalable gene synthesis and amplification of repetitive proteins
A codon-scrambling algorithm that exploits the codon redundancy of amino acids enables the high-throughput gene synthesis of repetitive proteins.
Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements
A detailed study of the effects of dCas9-KRAB-sgRNA complexes on enhancer activity, gene expression and heterochromatin formation shows high efficacy and specificity.
Through a proteomics approach, Qi and colleagues and Long and colleagues identify the sensor of the unfolded protein response IRE1α as an endogenous substrate of the E3 ubiquitin ligase involved in ER-associated degradation, Hrd1.
Intrinsically disordered protein polymers can be designed to encode tunable lower or upper critical solution temperatures in physiological solutions.
A paclitaxel-loaded recombinant polypeptide nanoparticle outperforms Abraxane in multiple murine cancer models
The encapsulation of a drug into nanoparticles can be a useful way control and improve its efficacy. Here, the authors conjugate paclitaxel to recombinant chimeric polypeptides that self-assemble into therapeutic nanoparticles that outperform Abraxane in murine tumour models.
Bacterial cells roughly double in size prior to each division but the process is inherently noisy and mechanisms ensuring cell size homeostasis are unknown. Now Lingchong You and colleagues have quantified single-cell growth over long periods of time in Escherichia coli, and describe transient oscillations with periods stretching across more than ten generations. Combining computer models with quantitative data, the authors propose a noisy negative feedback on cell-size control — small new-born cells tend to divide later than large new-born cells — with implications for the genetic and physiological processes required.
Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers
RNA-guided epigenome editing with Cas9 fused to an acetyltransferase domain activates gene expression through modification of promoters and enhancers.
Multiplex CRISPR/Cas9-based genome editing for correction of dystrophin mutations that cause Duchenne muscular dystrophy
Duchenne muscular dystrophy is caused by mutations in the dystrophin gene. Here, Ousterout et al. use multiplexed CRISPR/Cas9 genome editing to excise a large portion of the gene that carries over 60% of known dystrophin mutations. They show that this excision restores dystrophin expression in patient-derived cells.
Modification of the CRISPR/Cas9 genome editing system by the addition of the light inducible proteins CRY2 and CIBI1 enables blue light–mediated transcription of endogenous genes in mammalian cells.
The authors use developmental changes in chromatin accessibility to identify thousands of enhancer elements that are active at different postnatal developmental stages in granule neurons of the cerebellum. Zic transcription factors were found to promote gene expression patterns key for neuronal maturation by binding to late-acting enhancer elements.
The transcription factor E2F is critical for determining cell proliferation. By monitoring E2F activity in single cells throughout the cell cycle, Dong et al.provide evidence that Myc and G1 cyclin/CDKs regulate different aspects of E2F temporal dynamics, resulting in distinct phenotypic outputs.
Simultaneous transcranial magnetic stimulation and single-neuron recording in alert non-human primates
This Technical Report describes new methods of transcranial magnetic stimulation (TMS) in non-human primates. By combining single neuron recording with a modified TMS coil with focused stimulation in alert macaques, the authors show that this method can reduce stimulation artifact and allow investigation into the neuronal mechanisms of TMS.
Synthetic transcription factors based on the RNA-guided CRISPR-Cas9 system are used to activate specific endogenous genes in human cells. Also online, Joung and colleagues report similar developments at two other loci.
The combination of several TALE-TFs that bind the same gene promoter at different positions induces high and tunable activation, even in heterochromatic genes, and offers the promise of engineering complex synthetic gene expression systems.
In many photonic applications ranging from sensors to energy-harvesting devices, a perfectly absorbing material is desired. Previously, perfect absorbers of infrared or visible light have been made by using lithography to create patterned structures on metallic surfaces, but this approach is expensive and difficult to scale up. Antoine Moreau et al. have developed an attractively simple method, in which silver nanocubes produced by wet chemistry are randomly distributed across a polymer-coated gold surface. Each cube acts as a nanoantenna to counter the reflectance of the metal surface. These cubes are simple and cheap to produce and can be easily spread and attached to the surface, so that large areas can be covered. They provide a means of controlling the colour of the reflected light, and the efficient optical response of the cubes suggests that mixed cube populations with controlled sized dispersion could be used to adjust the absorption at will.
Using a new form of spectroscopic optical coherence tomography, researchers demonstrate three-dimensional molecular imaging of both endogenous and exogenous chromophores with high spectral fidelity. This scheme has significant implications for a range of biomedical applications, including ophthalmology, early cancer detection and understanding fundamental disease mechanisms such as hypoxia and angiogenesis.
Engineering biosynthetic excitable tissues from unexcitable cells for electrophysiological and cell therapy studies
Patch-clamp recordings are used to study the function of ion channels, but the method does not allow the assessment of tissue-level function. Kirkton and Bursac introduce a biosynthetic system for the study of channel activity and electrical conduction, facilitating studies of ion channel function.
High-throughput synthesis of long DNA molecules would open up new experimental paradigms in synthetic biology and functional genomics. Quan et al. take a step toward this goal by integrating oligonucleotide synthesis, amplification and gene assembly on a single microarray, and apply the technology to optimization of protein translation in a heterologous host.
A highly parallel method for synthesizing DNA repeats enables the discovery of ‘smart’ protein polymers
A one-pot, high-throughput method for the recombinant polymerization of monomer DNA sequences is reported. The method enables the rapid synthesis of diverse libraries of artificial repetitive polypeptides, exemplified by the isolation of protease-responsive polymers and a family of polypeptides with reversible thermally responsive behaviour.
In an effort to develop safer therapeutic agents and to limit unintended side effects, Sabah Oney and her colleagues have designed a set of antidote molecules for a series of aptamers exhibiting anticoagulant activities. These so-called universal antidotes are shown to sequester circulating aptamers and reverse their activity, irrespective of the primary sequence and folded structure of the aptamer.
Self-assembling chimeric polypeptide–doxorubicin conjugate nanoparticles that abolish tumours after a single injection
When artificial polypeptides are conjugated to a variety of hydrophobic molecules such as chemotherapeutics, the resulting molecules spontaneously self-assemble into nanoparticles. Delivering the chemotherapeutics to a murine cancer model, the nanoparticles have a fourfold higher maximum tolerated dose than the free drug, and induce nearly complete tumour regression after a single dose.