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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV-2 variants, has become a global pandemic resulting in significant morbidity and mortality. Severe cases of COVID-19 are characterized by hypoxemia, hyper-inflammation, cytokine storm in lung. Clinical studies have reported an association between COVID-19 and cardiovascular disease (CVD). Patients with CVD tend to develop severe symptoms and mortality if contracted COVID-19 with further elevations of cardiac injury biomarkers. Furthermore, COVID-19 itself can induce and promoted CVD development, including myocarditis, arrhythmia, acute coronary syndrome, cardiogenic shock, and venous thromboembolism. Although the direct etiology of SARS-CoV-2 induced cardiac injury remains unknown and under-investigated, it is suspected that it is related to myocarditis, cytokine-mediated injury, microvascular injury, and stress-related cardiomyopathy. Despite vaccinations having provided the most effective approach to reducing mortality overall, an adapted treatment paradigm and regular monitoring of cardiac injury biomarkers is critical for improving outcomes in vulnerable populations at risk for severe COVID-19. In this review, we focus on the latest progress in clinic and research on the cardiovascular complications of COVID-19 and provide a perspective of treating cardiac complications deriving from COVID-19 in Emergency Medicine., Competing Interests: Conflict of interest statement Xinliang Ma is the Associate Editor of Emergency and Critical Care Medicine, and Yajing Wang, Theodore A. Christopher, Bernard J. Lopez are Editorial Board members of Emergency and Critical Care Medicine. The article was subject to the journal’s standard procedures, with peer review handled independently of the Associate Editor, Editorial Board members, and their research groups. The authors declare no conflict of interest.

Competing Interests: The authors declare no conflict of interest.

We report an improved method for calibrating the nonlinear region of a single-beam gradient optical trap. Through analysis of the position fluctuations of a trapped object that is displaced from the trap center by controlled flow we measure the local trap stiffness in both the linear and nonlinear regimes without knowledge of the magnitude of the applied external forces. This approach requires only knowledge of the system temperature, and is especially useful for measurements involving trapped objects of unknown size, or objects in a fluid of unknown viscosity.

Using single-molecule fluorescence microscopy, we investigated the dynamics of dye-labeled EB1, a +TIP microtubule binding protein. To promote EB1 binding along the entire microtubule length, we formed microtubules using the nonhydrolyzable GTP analogs GMPCPP and GTPγS. Through precise tracking of the motions of individual dye-labeled proteins, we found EB1 to be highly dynamic and continuously diffusive while bound to a microtubule, with a diffusion coefficient and characteristic binding lifetime that were sensitive to both the choice of GTP analog and the buffer ionic strength. Using fluorescence-based equilibrium binding measurements, we found EB1 binding to be cooperative and also sensitive to GTP analog and ionic strength. By tracking the motion of a small number of individually-labeled EB1 proteins within a bath of unlabeled EB1 proteins, we determined the effects of increasing the total EB1 concentration on binding and dynamics. We found that the diffusion coefficient decreased with increasing EB1 concentration, which may be due at least in part, to the cooperativity of EB1 binding. Our results may have important consequences for the assembly and organization of the growing microtubule plus-end., (© 2015 Wiley Periodicals, Inc.)

In this article, we will summarize recent progress in understanding the mechanical origins of rigidity, strength, resiliency and stress transmission in the MT cytoskeleton using reconstituted networks formed from purified components. We focus on the role of network architecture, crosslinker compliance and dynamics, and molecular determinants of single filament elasticity, while highlighting open questions and future directions for this work., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Using the nonhydrolyzable GTP analog GMPCPP and the slowly hydrolyzable GTPγS, we polymerize microtubules that recapitulate the end binding behavior of the plus end interacting protein (+TIP) EB1 along their entire length, and use these to investigate the impact of EB1 binding on microtubule mechanics. To measure the stiffness of single filaments, we use a spectral analysis method to determine the ensemble of shapes adopted by a freely diffusing, fluorescently labeled microtubule. We find that the presence of EB1 can stiffen microtubules in a manner that depends on the hydrolysis state of the tubulin-bound nucleotide, as well as the presence of the small-molecule stabilizer paclitaxel. We find that the magnitude of the EB1-induced stiffening is not proportional to the EB1-microtubule binding affinity, suggesting that the stiffening effect does not arise purely from an increase in the total amount of bound EB1. Additionally, we find that EB1 binds cooperatively to microtubules in manner that depends on tubulin-bound nucleotide state., (© 2014 Wiley Periodicals, Inc.)

Cellular biopolymers can exhibit significant compositional heterogeneities as a result of the non-uniform binding of associated proteins, the formation of microstructural defects during filament assembly, or the imperfect bundling of filaments into composite structures of variable diameter. These can lead to significant variations in the local mechanical properties of biopolymers along their length. Existing spectral analysis methods assume filament homogeneity and therefore report only a single average stiffness for the entire filament. However, understanding how local effects modulate biopolymer mechanics in a spatially resolved manner is essential to understanding how binding and bundling proteins regulate biopolymer stiffness and function in cellular contexts. Here, we present a new method to determine the spatially varying material properties of individual complex biopolymers from the observation of passive thermal fluctuations of the filament conformation. We develop new statistical mechanics-based approaches for heterogeneous filaments that estimate local bending elasticities as a function of the filament arc-length. We validate this methodology using simulated polymers with known stiffness distributions, and find excellent agreement between derived and expected values. We then determine the bending elasticity of microtubule filaments of variable composition generated by repeated rounds of tubulin polymerization using either GTP or GMPCPP, a nonhydrolyzable GTP analog. Again, we find excellent agreement between mechanical and compositional heterogeneities.

Biomolecular motors have inspired the design and construction of artificial nanoscale motors and machines based on nucleic acids, small molecules, and inorganic nanostructures. However, the high degree of sophistication and efficiency of biomolecular motors, as well as their specific biological function, derives from the complexity afforded by protein building blocks. Here, we discuss a novel bottom-up approach to understanding biological motors by considering the construction of synthetic protein motors. Specifically, we present a design for a synthetic protein motor that moves along a linear track, dubbed the "Tumbleweed." This concept uses three discrete ligand-dependent DNA-binding domains to perform cyclically ligand-gated, rectified diffusion along a synthesized DNA molecule. Here we describe how de novo peptide design and molecular biology could be used to produce the Tumbleweed, and we explore the fundamental motor operation of such a design using numerical simulations. The construction of this and more sophisticated protein motors is an exciting challenge that is likely to enhance our understanding of the structure-function relationship in biological motors.

A flashing ratchet transports diffusive particles using a time-dependent, asymmetric potential. The particle speed is predicted to increase when a feedback algorithm based on the particle position is used. We have experimentally realized such a feedback ratchet using an optical line trap, and observed that use of feedback increases velocity by up to an order of magnitude. We compare two different feedback algorithms for small particle numbers, and find good agreement with simulations. We also find that existing algorithms can be improved to be more tolerant to feedback delay times.