A5069158023- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Muscle Physiology and Disorders
- Advanced Sensor and Energy Harvesting Materials
- Cardiovascular Function and Risk Factors
- Force Microscopy Techniques and Applications
- Molecular Junctions and Nanostructures
- Pulmonary Hypertension Research and Treatments
- Genetic Neurodegenerative Diseases
- Cancer Cells and Metastasis
- Pancreatic and Hepatic Oncology Research
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Cardiac Structural Anomalies and Repair
- Gastric Cancer Management and Outcomes
- Heart Failure Treatment and Management
- Antibiotic Resistance in Bacteria
Illinois Institute of Technology
2019-2024
Abstract Muscle contraction is produced via the interaction of myofilaments and regulated so that muscle performance matches demand. Myosin-binding protein C (MyBP-C) a long flexible tightly bound to thick filament at its C-terminal end (MyBP-C C8C10 ), but may be loosely middle- N-terminal C1C7 ) myosin heads and/or thin filament. MyBP-C thought control regulation motors, as mutations lead debilitating disease. We use combination mechanics small-angle X-ray diffraction study immediate...
Skeletal muscle force production is increased at longer compared to shorter lengths because of length-dependent priming thick filament proteins in the contractile unit before contraction. Using small-angle X-ray diffraction combination with a mouse model that specifically cleaves stretch-sensitive titin protein, we found cleavage diminished filament. Strikingly, titin-sensitive, was also present thin filaments, which seems only possible via bridge between and filaments resting muscle,...
Right ventricular (RV) contractile dysfunction commonly occurs and worsens outcomes in patients with heart failure reduced ejection fraction pulmonary hypertension (HFrEF-PH). However, such often goes undetected by standard clinical RV indices, raising concerns that they may not reflect aspects of underlying myocyte dysfunction. We thus sought to characterize depression HFrEF-PH, identify those components reflected uncover biophysical mechanisms.
Hypertrophic cardiomyopathy (HCM) is a genetic disease of the heart characterized by thickening left ventricle (LV), hypercontractility, and impaired relaxation. HCM caused primarily heritable mutations in sarcomeric proteins, such as β myosin heavy chain. Until recently, medications clinical use for did not directly target underlying contractile changes sarcomere. Here, we investigate novel small molecule, RLC-1, identified bovine cardiac myofibril high-throughput screen. RLC-1 highly...
In muscle, titin proteins connect myofilaments together and are thought to be critical for contraction, especially during residual force enhancement (RFE) when steady-state is elevated after an active stretch. We investigated titin’s function contraction using small-angle X-ray diffraction track structural changes before 50% cleavage in the RFE-deficient, mdm mutant. report that RFE state structurally distinct from pure isometric contractions, with increased thick filament strain decreased...
In muscle, titin proteins connect myofilaments together and are thought to be critical for contraction, especially during residual force enhancement (RFE) when is elevated after an active stretch. We investigated titin's function contraction using small-angle X-ray diffraction track structural changes before 50% cleavage in the RFE-deficient, mdm mutant. report that RFE state structurally distinct from pure isometric contractions, with increased thick filament strain decreased lattice...
The first-in-its-class cardiac drug mavacamten reduces the proportion of so-called ON-state myosin heads in relaxed sarcomeres, altering contraction performance. However, is not completely specific to and can also affect skeletal muscle myosin, an important consideration since administered orally so will be present tissue. Here, we studied effect on structure using small-angle X-ray diffraction. Mavacamten treatment reduced ON but did eliminate molecular underpinnings length-dependent...
Right ventricular (RV) contractile dysfunction commonly occurs and worsens outcomes in heart failure patients with reduced ejection fraction pulmonary hypertension (HFrEF-PH). However, such often goes undetected by standard clinical RV indices, raising concerns that they may not reflect aspects of underlying myocyte dysfunction.To determine components depression HFrEF-PH, identify those reflected elucidate their biophysical mechanisms.Resting, calcium- load-dependent mechanics were measured...
Pancreatic ductal adenocarcinomas (PDACs) are often treatment resistant, and as such widefield imaging methods for the evaluation of ECM composition needed. Here we present a method to measure relative abundance diffracting components in PDAC samples alongside drug penetration images. Orthotopic mouse xenografts grown assessment well is done using co-registration scanning x-ray diffraction (XRD) EGFR-specific fluorescent Preliminary data suggests strongly negative correlation between large...
Contraction force in muscle is produced by the interaction of myosin motors thick filaments and actin thin fine-tuned other proteins such as myosin-binding protein C (MyBP-C). One form control through regulation heads between an ON OFF state passive sarcomeres, which leads to their ability or inability interact with during contraction, respectively. MyBP-C a flexible long that tightly bound filament at its C-terminal end but may be loosely middle- N-terminal (MyBP-CC1C7). Under considerable...
Significance: While the disease mechanisms of truncating MyBP-C variants in HCM have been well defined, by which missense cause are largely unknown. Recent studies show that unlike push myosin into an active high energy state due to their overall reduction MyBP-C, properly incorporates sarcomere without affecting protein abundance. The consequences on not explored and may implications for treatment patients with variants. Results: We performed small angle X-ray diffraction (XrD) human tissue...
Abstract The Frank-Starling law states that the heart’s stroke volume increases with greater preload due to increased venous return, allowing heart adapt varying circulatory demands. Molecularly, increasing sarcomere length (SL), which alters structures are correlated calcium sensitivity upon activation. titin protein, spanning half-sarcomere, acts as a spring in I-band, applying SL-dependent force suggested pull against and alter myofilaments way supports effect. To evaluate this, we...
Intro: Right ventricular (RV) dysfunction worsens outcomes in pulmonary hypertension (PH) due to heart failure with reduced ejection fraction (HF), yet underlying mechanisms are unknown. We previously reported RV myofilament max calcium-activated tension (T ) is human PH-HF. Here, we reveal that this decline more myosin heads the super-relaxed (SRX) state which lack force-production low ATP turnover. Methods: Frozen myocardium from 25 PH-HF and 9 control patients were permeabilized myocyte...