Progression of Mitochondrial Network Dysfunction in Cardiomyocytes and the Arrhythmogenic Implications: A Computational Study

Dense, tightly coupled networks, found throughout nature are vulnerable to cascading failure, where a small increase in stress can create a decrease in performance across the whole network. Mitochondria exist as dense networks within cardiomyocytes to meet the large energetic demands of heart function but are vulnerable to excessive oxidative stress such as during ischemia/reperfusion. Arrhythmia are observed in hearts exposed to oxidative stress and they occur just after the mitochondrial network within the tissue fails, suggesting an arrhythmogenic role of mitochondrial failure. This work investigates the mechanisms underlying the progression of mitochondrial network failure and how this failure can scale to the whole heart. A computational modeling approach was used to study the complex systems existing at multiple spatial and temporal scales. First, a mitochondrial network model was developed, where mitochondria were coupled by diffusion of reactive oxygen species (ROS) including superoxide and hydrogen peroxide. The simulation results revealed that while superoxide was important for propagating mitochondrial depolarizations across the network, diffusion of hydrogen peroxide was required for extending the failure region to the rest of the network. Failure of the network could not occur until depletion of the network's scavenging capacity, which superoxide alone could not induce because of its periodic release. Second, a ventricular myocyte model that included a mitochondrial component was incorporated into a 2D tissue model to study how oscillation of mitochondrial membrane potential can create reentry. A large enough region of tissue with depolarized mitochondria had lower ATP levels, and activated ATP sensitive potassium channels that reduced their excitability and shortened their action potential duration (APD). Upon repolarization of the mitochondria, the tissue became excitable and an existing propagating wave was able to spontaneously propagate in reverse, creating reentry. Together, these findings demonstrate the link between mitochondrial failure and arrhythmia, through the emergence of complex, arrhythmogenic spatiotemporal patterns of excitability. This research provides new potential targets for pharmaceutical intervention that may be used to prevent post-ischemic arrhythmia such as from a myocardial infarction

Print-and-Peel Fabrication for Microfluidics: What’s in it for Biomedical Applications?

This article reviews the development and the advances of print-and-peel (PAP) microfabrication. PAP techniques provide means for facile and expedient prototyping of microfluidic devices. Therefore, PAP has the potential for broadening the microfluidics technology by bringing it to researchers who lack regular or any accesses to specialized fabrication facilities and equipment. Microfluidics have, indeed, proven to be an indispensable toolkit for biological and biomedical research and development. Through accessibility to such methodologies for relatively fast and easy prototyping, PAP has the potential to considerably accelerate the impacts of microfluidics on the biological sciences and engineering. In summary, PAP encompasses: (1) direct printing of the masters for casting polymer device components; and (2) adding three-dimensional elements onto the masters for single-molding-step formation of channels and cavities within the bulk of the polymer slabs. Comparative discussions of the different PAP techniques, along with the current challenges and approaches for addressing them, outline the perspectives for PAP and how it can be readily adopted by a broad range of scientists and engineers

Permanent Electric Dipole Moments of Carboxyamides in Condensed Media: What Are the Limitations of Theory and Experiment?

Electrostatic properties of proteins are crucial for their functionality. Carboxyamides are small polar groups that, as peptide bonds, are principal structural components of proteins that govern their electrostatic properties. We investigated the medium dependence of the molar polarization and of the permanent dipole moments of amides with different state of alkylation. The experimentally measured and theoretically calculated dipole moments manifested a solvent dependence that increased with the increase in the media polarity. We ascribed the observed enhancement of the amide polarization to the reaction fields in the solvated cavities. Chloroform, for example, caused about a 25% increase in the amide dipole moments determined for vacuum, as the experimental and theoretical results demonstrated. Another chlorinated solvent, 1,1,2,2-tetrachloroethane, however, caused an "abnormal" increase in the experimentally measured amide dipoles, which the theoretical approaches we used could not readily quantify. We showed and discussed alternatives for addressing such discrepancies between theory and experiment