Simultaneous electromechanical monitoring in engineered heart tissues using a mesoscale framework.

Engineered heart tissues (EHTs) generated from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent powerful platforms for human cardiac research, especially in drug testing and disease modeling. Here, we report a flexible, three-dimensional electronic framework that enables real-time, spatiotemporal analysis of electrophysiologic and mechanical signals in EHTs under physiological loading conditions for dynamic, noninvasive, longer-term assessments. These electromechanically monitored EHTs support multisite measurements throughout the tissue under baseline conditions and in response to stimuli.

Susceptibility to innate immune activation in genetically mediated myocarditis.

Myocarditis is clinically characterized by chest pain, arrhythmias, and heart failure, and treatment is often supportive. Mutations in DSP, a gene encoding the desmosomal protein desmoplakin, have been increasingly implicated in myocarditis. To model DSP-associated myocarditis and assess the role of innate immunity, we generated engineered heart tissues (EHTs) using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from patients with heterozygous DSP truncating variants (DSPtvs) and a gene-edited homozygous deletion cell line (DSP-/-).

Physiological stress improves stem cell modeling of dystrophic cardiomyopathy.

Heart failure contributes to Duchenne muscular dystrophy (DMD), which arises from mutations that ablate dystrophin, rendering the plasma membrane prone to disruption. Cardiomyocyte membrane breakdown in patients with DMD yields a serum injury profile similar to other types of myocardial injury with the release of creatine kinase and troponin isoforms. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are highly useful but can be improved.

Genetic Variation in Enhancers Modifies Cardiomyopathy Gene Expression and Progression.

Background: Inherited cardiomyopathy associates with a range of phenotypes, mediated by genetic and nongenetic factors. Noninherited cardiomyopathy also displays varying progression and outcomes. Expression of cardiomyopathy genes is under the regulatory control of promoters and enhancers, and human genetic variation in promoters and enhancers may contribute to this variability.

pH-dependent cross-linking of catechols through oxidation via Fe and potential implications for mussel adhesion.

The mussel byssus is a remarkable attachment structure that is formed by injection molding and rapid in-situ hardening of concentrated solutions of proteins enriched in the catecholic amino acid 3,4-dihydroxy-L-phenylalanine (DOPA). Fe, found in high concentrations in the byssus, has been speculated to participate in redox reactions with DOPA that lead to protein polymerization, however direct evidence to support this hypothesis has been lacking. Using small molecule catechols, DOPA-containing peptides, and native mussel foot proteins, we report the first direct observation of catechol oxidation and polymerization accompanied by reduction of Fe to Fe.

Metal-coordination: Using one of nature's tricks to control soft material mechanics.

Growing evidence supports a critical role of dynamic metal-coordination crosslinking in soft biological material properties such as self-healing and underwater adhesion. Using bio-inspired metal-coordinating polymers, initial efforts to mimic these properties have shown promise. Here we demonstrate how bio-inspired aqueous polymer network mechanics can be easily controlled via metal-coordination crosslink dynamics; metal ion-based crosslink stability control allows aqueous polymer network relaxation times to be finely tuned over several orders of magnitude.

pH-Based Regulation of Hydrogel Mechanical Properties Through Mussel-Inspired Chemistry and Processing.

The mechanical holdfast of the mussel, the byssus, is processed at acidic pH yet functions at alkaline pH. Byssi are enriched in Fe and catechol-containing proteins, species with chemical interactions that vary widely over the pH range of byssal processing. Currently, the link between pH, Fe-catechol reactions, and mechanical function are poorly understood.

Mussel-inspired histidine-based transient network metal coordination hydrogels.

Transient network hydrogels cross-linked through histidine-divalent cation coordination bonds were studied by conventional rheologic methods using histidine-modified star poly(ethylene glycol) (PEG) polymers. These materials were inspired by the mussel, which is thought to use histidine-metal coordination bonds to impart self-healing properties in the mussel byssal thread. Hydrogel viscoelastic mechanical properties were studied as a function of metal, pH, concentration, and ionic strength.

Mussel-inspired silver-releasing antibacterial hydrogels.

A silver-releasing antibacterial hydrogel was developed that simultaneously allowed for silver nanoparticle formation and gel curing. Water-soluble polyethylene glycol (PEG) polymers were synthesized that contain reactive catechol moieties, inspired by mussel adhesive proteins, where the catechol containing amino acid 3,4-dihydroxyphenylalanine (DOPA) plays an important role in the ability of the mussel to adhere to almost any surface in an aqueous environment. We utilized silver nitrate to oxidize polymer catechols, leading to covalent cross-linking and hydrogel formation with simultaneous reduction of Ag(I).

pH responsive self-healing hydrogels formed by boronate-catechol complexation.

Here we report the synthesis and characterization of pH-responsive, self-healing hydrogels based on boronate-catechol complexation.

Quantitative angle-resolved SPR imaging of DNA-DNA and DNA-drug kinetics.

We demonstrate the quantitative characterization of DNA-DNA and DNA-drug interactions by angle-resolved surface plasmon resonance (SPR) imaging. Combining the angle-scanning capabilities of traditional SPR with the spatial definition capabilities of imaging, we directly measure DNA and drug surface coverages and kinetics simultaneously for multiple patterned spots. We find excellent agreement of DNA-DNA hybridization kinetics and thermodynamics measured by both the imaging system and traditional SPR.