Cell Biology Commons^™

Identification Of Tectorigenin As A Natural Pro-Hypoxia Compound: Implications In Modulation Of Cellular Differentiation And Senescence, Mallika Khurana, Renu Wadhwa, Sunil Kaul

Research Symposium

Background: Hypoxia, a suboptimal level of oxygen, evokes stress response in cells and activated hypoxia signaling has been largely established as a pro-metastasis and pro-angiogenic factor for tumor cells. On the other hand, age-related neurodegenerative disorders are characterized by hypoxic environment, accumulation of molecular garbage and induction of premature senescence. Several recent studies have reported anti-stress impact of the intermittent induction of hypoxia signaling in these cells.

Methods: Screening of a phytochemical library using Hypoxia Responsive Element (HRE) driven luciferase as a reporter was carried out to identify hypoxia-modulating phytochemicals. Activation of HIF-1a (master regulator of hypoxia signaling) was validated …

Identification Of The Functional Domain Of The Dense Core Vesicle Biogenesis Factor Hid-1, Blake H. Hummer, Theodore Carter, Breanna L. Sellers, Jenna D. Triplett, Cedric S. Asensio

Biological Sciences: Faculty Scholarship

Large dense core vesicles (LDCVs) mediate the regulated release of neuropeptides and peptide hormones. HID-1 is a trans-Golgi network (TGN) localized peripheral membrane protein contributing to LDCV formation. There is no information about HID-1 structure or domain architecture, and thus it remains unknown how HID-1 binds to the TGN and performs its function. We report that the N-terminus of HID-1 mediates membrane binding through a myristoyl group with a polybasic amino acid patch but lacks specificity for the TGN. In addition, we show that the C-terminus serves as the functional domain. Indeed, this isolated domain, when tethered to the TGN, …

Tmem27 Suppresses Tumor Development By Promoting Ret Ubiquitination, Positioning, And Degradation, Qianjin Guo, Zi-Ming Cheng, Hector Gonzalez-Cantú, Matthew Rotondi, Gabriela Huelgas-Morales, Purushoth Ethiraj, Zhijun Qiu, Jonathan Lefkowitz, Wan Song, Bethany N Landry, Hector Lopez, Cynthia M Estrada-Zuniga, Shivi Goyal, Mohammad Aasif Khan, Timothy J Walker, Exing Wang, Faqian Li, Yanli Ding, Lois M Mulligan, Ricardo C T Aguiar, Patricia L M Dahia

Journal Articles

The TMEM127 gene encodes a transmembrane protein of poorly known function that is mutated in pheochromocytomas, neural crest-derived tumors of adrenomedullary cells. Here, we report that, at single-nucleus resolution, TMEM127-mutant tumors share precursor cells and transcription regulatory elements with pheochromocytomas carrying mutations of the tyrosine kinase receptor RET. Additionally, TMEM127-mutant pheochromocytomas, human cells, and mouse knockout models of TMEM127 accumulate RET and increase its signaling. TMEM127 contributes to RET cellular positioning, trafficking, and lysosome-mediated degradation. Mechanistically, TMEM127 binds to RET and recruits the NEDD4 E3 ubiquitin ligase for RET ubiquitination and degradation via TMEM127 C-terminal PxxY motifs. Lastly, increased cell …

Effects Of Osmotic Stress On Oxygen Consumption Of Drosophila Cells (Kc167), Ali A. Ahmed, Rajib Hassan, Michael A. Menze

The Cardinal Edge

This article investigates the effect of osmotic stress on a drosophila cell line called Kc167.

The embryonic-derived fly (Drosophila melanogaster) cell line, Kc-167, was employed as a model for water-stress sensitivity in Arthropods. Like mammalian cells, cells derived from the fruit fly contain the same basic set of membranous components found in all eukaryotic cells. A series of experiments were conducted to characterize the mitochondrial repones of Kc167 cells to water stress. Precisely, the oxygen flux in a sealed respirometer chamber containing Kc167 cells was measured under hyperosmotic and control conditions. Mitochondrial uncouplers were used in some experiments for intact …

Examining Pi3k-Signaling-Dependent Regulation Of Lens Organelle Free Zone Formation Via Immunolocalization And Immunoblotting In Chick Embryos, Rifah Gheyas, A. Sue Menko

Computational Medicine Center Faculty Papers

The elimination of lens organelles during development, required for mature lens function, is an autophagy-dependent mechanism induced through suppression of PI3K signaling. Here, we present a protocol for investigating the signaling pathways responsible for induction of the formation of this lens organelle free zone. We describe steps for preparation of lens organ culture and use of signaling pathway inhibitors. We then detail procedures for analyzing their impact using both confocal microscopy imaging of immunolabeled lens cryosections and immunoblot approaches. For complete details on the use and execution of this protocol, please refer to Gheyas et al. (2022).

Canine Testes Thin Sections Culture​, Nguyen Khoi Nguyen, Ramanpreet Singh

2023 Symposium

Canine testes thin section culture

Testes tissue culture systems would provide a tool to elucidate spermatogenesis mechanisms, with the aim of genetic preservation of mammals, especially endangered species. Our experiment aims to develop a culture system capable of producing viable mammalian sperm cells in vitro.

Dogs were chosen as the model organism because testes are readily available. Canine testes were obtained from a local veterinary clinic. Thin sections were generated using a commercial electric slicer. They then were cleaned using Dulbecco’s Phosphate-Buffered Saline (DPBS) supplemented with antibiotics then cultured in a modified Tissue Culture Medium 199 (TCM-199). Sections were …

Canine Testes Thin Sections Culture, Nguyen Khoi Nguyen, Ramanpreet Singh

2023 Symposium

Canine testes thin section culture

Testes tissue culture systems would provide a tool to elucidate spermatogenesis mechanisms, with the aim of genetic preservation of mammals, especially endangered species. Our experiment aims to develop a culture system capable of producing viable mammalian sperm cells in vitro.

Dogs were chosen as the model organism because testes are readily available. Canine testes were obtained from a local veterinary clinic. Thin sections were generated using a commercial electric slicer. They then were cleaned using Dulbecco’s Phosphate-Buffered Saline (DPBS) supplemented with antibiotics then cultured in a modified Tissue Culture Medium 199 (TCM-199). Sections were …

Oligodendrocyte 2phatal Reveals Dynamics Of Myelin Degeneration And Repair, Timothy W. Chapman

Dartmouth College Ph.D Dissertations

Oligodendrocytes are responsible for producing myelin in the central nervous system. This lipid-rich coating along axons helps to increase action potential velocity, provide metabolic support to axons, and facilitate fine-tuning of neuronal circuitry. Demyelination and/or myelin dysfunction is widespread in neurodegenerative diseases and aging. Despite this, we know very little about how individual oligodendrocytes, or the myelin sheaths they produce, degenerate. Myelin repair, carried out by resident oligodendrocyte precursor cells (OPCs), is known to occur following myelin damage in certain contexts. We sought to investigate the cellular dynamics of oligodendrocyte degeneration and repair by developing a non-inflammatory demyelination model, combining …

Transcriptional Pausing Factor M1bp Regulates Cellular Homeostasis By Suppressing Autophagy And Apoptosis In Drosophila Eye, Anuradha Venkatakrishnan Chimata, Hannah Darnell, Akanksha Raj, Madhuri Kango-Singh

Biology Faculty Publications

During organogenesis cellular homeostasis plays a crucial role in patterning and growth. The role of promoter proximal pausing of RNA polymerase II, which regulates transcription of several developmental genes by GAGA factor or Motif 1 Binding Protein (M1BP), has not been fully understood in cellular homeostasis. Earlier, we reported that M1BP, a functional homolog of ZKSCAN3, regulates wingless (wg) and caspase-dependent cell death (apoptosis) in the Drosophila eye. Further, blocking apoptosis does not fully rescue the M1BP^RNAi phenotype of reduced eye. Therefore, we looked for other possible mechanism(s). In a forward genetic screen, members of the Jun-amino-terminal-(NH2)-Kinase (JNK) pathway …

Age-Related Morphofunctional Changes In Sickle Cell Mice Bone Marrow Mesenchymal Stromal Cells, Felipe Augusto Rós, Péricles Natan Mendes Da Costa, Jonathan Milhomens, Débora Glenda Lima De La-Roque, Fernanda Ursoli Ferreira, Juliana De Matos Maçonetto, Camila Cristina De Oliveira Menezes Bonaldo, Julianne Vargas De Carvalho, Patrícia Vianna Bonini Palmaa Palma, Wassim El Nemer, Dimas Tadeu Covas, Simone Kashima

Hematology/Oncology and Stem Cell Therapy

Bone marrow mesenchymal stromal cells (BM-MSC) are key elements of the hematopoietic niche and participate in the regulatory mechanisms of hematopoietic stem cells (HSC). Hematological diseases can affect MSCs and their functions. However, the dysregulations caused by sickle cell disease (SCD) are not fully elucidated. This work explored changes in BM-MSC and their relationship with age using sickle cell mice (Townes-SS). BM-MSC were isolated from Townes-SS, and control groups Townes-AA and C57BL/6J at 30- and 60-day-old. The BM-MSCs showed no morphological differences in culture and demonstrated the murine MSC-like immunophenotypic profile (Sca-1+, CD29+, CD44+, CD90.2+, CD31-, CD45- and CD117-). Subsequently, …

Endothelial Interleukin-17 Receptor D (Il17rd) Promotes Western Diet-Induced Aortic Myeloid Cell Infiltration, Shivangi Pande

Electronic Theses and Dissertations

The Interleukin-17 (IL17) family is a group of cytokines implicated in the etiology of several inflammatory diseases. Interleukin-17 receptor D (IL17RD), also known as Sef (similar expression to fibroblast growth factor), belonging to the family of IL17 receptors, has been shown to modulate IL17A-associated inflammatory phenotypes. The objective of this study was to test the hypothesis that IL17RD promotes endothelial cell activation and consequent monocyte adhesion. We utilized primary human aortic endothelial cells and demonstrated that RNAi targeting of IL17RD suppressed transcript levels by 83% compared to non-targeted controls. Further, RNAi knockdown of IL17RD decreased the adhesion of THP-1 cells …

Profiling And Verifying The Substrates Of E3 Ubiquitin Ligase Rsp5 In Yeast Cells, Shuai Fang, Geng Chen, Yiyang Wang, Rakhee Ganti, Tatiana A Chernova, Li Zhou, Savannah E Jacobs, Duc Duong, Hiroaki Kiyokawa, Yury O Chernoff, Ming Li, Natalia Shcherbik, Bo Zhao, Jun Yin

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Yeast is an essential model organism for studying protein ubiquitination pathways; however, identifying the direct substrates of E3 in the cell presents a challenge. Here, we present a protocol for using the orthogonal ubiquitin transfer (OUT) cascade to profile the substrate specificity of yeast E3 Rsp5. We describe steps for OUT profiling, proteomics analysis, in vitro and in cell ubiquitination, and stability assay. The protocol can be adapted for identifying and verifying the ubiquitination targets of other E3s in yeast. For complete details on the use and execution of this protocol, please refer to Wang et al.

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …

A Comparison Of Pm-Nato3’S Influence On Neural Progenitors And Mature Dopamine Neurons, Mary E. West

Masters Theses

This thesis presents significant findings regarding the role of PM-Nato3 in its interaction with developing neurons in the context of Parkinson's disease (PD) and regenerative medicine. We investigated the effects of PM-Nato3 on dopamine (DA) neurogenesis under different culture conditions, both in vitro and in vivo. In the standard dopaminergic culture condition, PM-Nato3 potentially increased the speed of DA neuron production but did not significantly increase the yield of DA neurons. In a minimal culture condition, there was no notable difference between the control and PM-Nato3 conditions, suggesting minimal impact on DA neurogenesis. In vivo studies using a mouse model …

Photodynamic Therapy To Treat Triple Negative Breast Cancer In Vitro, Hunter S. Warren

All Theses

Triple negative breast cancer (TNBC) is the most resilient form of breast cancer, being one of the leading causes of death for women and making up 7% of all cancer deaths. Photodynamic therapy (PDT) offers a minimally invasive solution to TNBC as a passive-targeting treatment that reduces the need for other well established yet harsh treatments that can be taxing on the patient. PDT involves the use of a high-energy red light on the area of a tumor injected with photosensitizers (PS) that generate reactive oxygen species (ROS) in the tumor, triggering cell death. The PS tetra(hydroxyphenyl)chlorin (m-THPC) was used …

Investigating The Role Of Il-10 Producing Nkt Cells In Prevention Of Graft Versus Host Disease, Drew Boagni

Dissertations & Theses (Open Access)

The standard curative treatment for hematologic malignancies is allogeneic stem cell transplantation (ASCT), in which the patient’s immune system is replaced with that of a healthy donor. This can lead to cure through the graft versus leukemia (GVL) effect but can also cause graft versus host disease (GVHD), which is characterized by systemic inflammation and organ damage mediated by dysregulated donor T cells. Preclinical studies have shown invariant natural killer T cells (iNKT) cells can prevent GVHD while preserving GVL. iNKT cells are unconventional T cells which recognize glycolipid antigens presented in the context of CD1d. Upon activation, they secrete …

Modeling Biphasic, Non-Sigmoidal Dose-Response Relationships: Comparison Of Brain- Cousens And Cedergreen Models For A Biochemical Dataset, Venkat D. Abbaraju, Tamaraty L. Robinson, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Biphasic, non-sigmoidal dose-response relationships are frequently observed in biochemistry and pharmacology, but they are not always analyzed with appropriate statistical methods. Here, we examine curve fitting methods for “hormetic” dose-response relationships where low and high doses of an effector produce opposite responses. We provide the full dataset used for modeling, and we provide the code for analyzing the dataset in SAS using two established mathematical models of hormesis, the Brain-Cousens model and the Cedergreen model. We show how to obtain and interpret curve parameters such as the ED50 that arise from modeling, and we discuss how curve parameters might change …

Studying The Stability Of Collagen/Heparin Coatings To Be Used In Cell Therapy Applications, Gavin Mussino

Biological Sciences Undergraduate Honors Theses

This honors thesis aims to investigate the reusability and performance of cell coatings for cell therapy applications. Cell therapy, which involves the use of human cells to repair or replace damaged tissues, holds immense potential for medical advancements. However, ensuring the survival and functionality of transplanted cells remains a significant challenge. We focused on studying the effectiveness of coatings applied to cells for improved cell growth and viability. The research project involved the preparation of the coatings using a layer-by-layer method and the subsequent seeding of cells. The coated cells were then subjected to a series of experiments to assess …

The Role Of Adenovirus Serotype 5 E4 11k In The Relocalization Of The Cellular P Body Proteins, Kasey A. Karen, La`Quita Randolph, Kevin Neubrecht, Heather Vincent

Georgia Journal of Science

Human adenoviruses are a useful tool to understand basic cellular biology in addition to viral infections. Historically, cellular splicing was first discovered in adenovirus, but other cellular processes, such as double-strand break repair and aggresome formation, have been further elucidated through adenoviral infection. The adenovirus protein E4 11k has been shown to disrupt cytoplasmic processing bodies (p bodies), which are not well-understood but are involved in mRNA metabolism. Several p body proteins were found to be reorganized in the cytoplasm with adenovirus serotype 5 (Ad5) able to cause the colocalization of these p body proteins with aggresomes. The p body …

N-Acetyltransferase 9 Ameliorates Aβ42-Mediated Neurodegeneration In The Drosophila Eye, Prajakta Deshpande, Anuradha Venkatakrishnan Chimata, Emily E. Snider, Aditi Singh, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, manifests as accumulation of amyloid-beta-42 (Aβ42) plaques and intracellular accumulation of neurofibrillary tangles (NFTs) that results in microtubule destabilization. Targeted expression of human Aβ42 (GMR > Aβ42) in developing Drosophila eye retinal neurons results in Aβ42 plaque(s) and mimics AD-like extensive neurodegeneration. However, there remains a gap in our understanding of the underlying mechanism(s) for Aβ42-mediated neurodegeneration. To address this gap in information, we conducted a forward genetic screen, and identified N-acetyltransferase 9 (Mnat9) as a genetic modifier of GMR > Aβ42 neurodegenerative phenotype. Mnat9 is known to stabilize microtubules by inhibiting c-Jun-N- …

Examining Protein Localization Via Fluorescence Microscopy In Saccharomyces Cerevisiae, Lewis Barr, Richard H. Adams, Ellen France Phd

Biology Theses

Twenty-seven years ago, Saccharomyces cerevisiae became the first eukaryote to have its full genome sequenced, thus leading to the discovery that 30% of genes related to human diseases are orthologous to those in S. cerevisiae. Since then, 75% of the proteome has had its localization classified, and we sought to fill the remaining gaps of knowledge by identifying the localization of three proteins: Fsh3, Gid10, and Ade13, which function as a serine hydrolase, ubiquitin ligase, and adenylosuccinate lyase, respectively. To visualize cellular localization, we used a C-terminal GFP tagging strategy and subsequent fluorescence microscopy. Through colocalization analyses, we identified …

Elucidating The Biomechanics Of Mertk-Mediated Efferocytosis, Brandon Hayato Dickson

Electronic Thesis and Dissertation Repository

Macrophages are key mediators of efferocytosis – the phagocytic engulfment and removal of apoptotic cells. During engulfment, the coordinated activity of efferocytic receptors induces the remodeling of the actin cytoskeleton, which facilitates the envelopment of the cell by the plasma membrane. Mer receptor tyrosine kinase (MERTK) is a crucial efferocytic receptor, but its role during actin remodeling is not well understood. Previously, our lab showed that MERTK is an activator of β₂ integrins – which are comprised of receptors known to induce the actin polymerization that is required for engulfment. We hypothesized that MERTK is an indirect stimulator of …

Proteomic Approaches To Identify Unique And Shared Substrates Among Kinase Family Members, Charles Lincoln Howarth

Dartmouth College Ph.D Dissertations

Protein phosphorylation is a reversible post-translational modification that is a critical component of almost all signaling pathways. Kinases regulate substrate proteins through phosphorylation, and nearly all proteins are phosphorylated to some extent. Crucially, breakdown in phosphorylation signaling is an underlying factor in many diseases, including cancer. Understanding how phosphorylation signaling mediates cellular pathways is crucial for understanding cell biology and human disease.

Targeted protein degradation (TPD) is a strategy to rapidly deplete a protein of interest (POI) and is applicable to any gene that is amenable to CRISPR-Cas9 editing. One TPD approach is the auxin-inducible degron (AID) system, which relies …

Recovery From Social Isolation In Drosophila: The Role Of Dopamine And The Autism-Related Gene Nlg3., Ryley T. Yost

Electronic Thesis and Dissertation Repository

Within a group, individuals establish their preferred distance from each other, or social space, a form of social behaviour. The resulting distance depends on the exchange of social cues from others that needs to be perceived and integrated within the organism’s neural circuitry. In humans, social spacing can be impaired in neuropsychiatric disorders such as autism and schizophrenia. When organisms are subject to social isolation, profound changes in social behaviour are observed in a variety of species from insects to mammals, including social space. However, the genetic and molecular mechanisms modulating a behavioural response to isolation and possible recovery remain …

Fibrosis-The Tale Of H3k27 Histone Methyltransferases And Demethylases, Morgan D. Basta, Svetlana Petruk, Alexander Mazo, Janice L. Walker

Department of Biochemistry and Molecular Biology Faculty Papers

Fibrosis, or excessive scarring, is characterized by the emergence of alpha-smooth muscle actin (αSMA)-expressing myofibroblasts and the excessive accumulation of fibrotic extracellular matrix (ECM). Currently, there is a lack of effective treatment options for fibrosis, highlighting an unmet need to identify new therapeutic targets. The acquisition of a fibrotic phenotype is associated with changes in chromatin structure, a key determinant of gene transcription activation and repression. The major repressive histone mark, H3K27me3, has been linked to dynamic changes in gene expression in fibrosis through alterations in chromatin structure. H3K27-specific homologous histone methylase (HMT) enzymes, Enhancer of zeste 1 and 2 …

Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi-Yang Peng, Rui Wang, Xiang Li, Ning Du, Da-Peng Liu, Jia Zhang, Yun-Feng Zhang, Lei Ma, Ye Sun, Shou-Ching Tang, Hong Ren, Yi-Ping Yang, Xin Sun

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem.

METHODS: By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing …

Regulation Of The Wnt/Wingless Receptor Lrp6/Arrow By The Deubiquitylating Complex Usp46, Zachary T. Spencer

Dartmouth College Ph.D Dissertations

The evolutionarily conserved Wnt/Wingless signal transduction pathway is critical for the proper development of all animals and implicated in numerous diseases in adulthood. Upon binding of the Wnt/Wingless ligand, a cascade of events culminates in inactivation of the destruction complex, a negative regulator of the pathway, and the subsequent formation of singalosomes which mediate pathway activation. A critical component of signalosome formation is the Wnt/Wingless receptor LRP6/Arrow. Upon canonical pathway activation, LRP6/Arrow undergoes activation via phosphorylation by several kinases and complexes with another Wnt/Wingless receptor Frizzled, along with several cytoplasmic components. While many studies have investigated the regulatory mechanisms of …

The Pros Of Changing Trna Identity, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The notion that errors in protein synthesis are universally harmful to the cell has been questioned by findings that suggest such mistakes may sometimes be beneficial. However, how often these beneficial mistakes arise from programmed changes in gene expression as opposed to reduced accuracy of the translation machinery is still unclear. A new study published in JBC shows that some bacteria have beneficially evolved the ability to mistranslate specific parts of the genetic code, a trait that allows improved antibiotic resistance.

Exploring Strain Variation And Bacteriophage Predation In The Gut Microbiome Of Ciona Robusta, Celine Grace F. Atkinson

USF Tampa Graduate Theses and Dissertations

Current microbiome studies have shown that the maintenance of homeostasis betweenmicrobial populations (e.g. bacteria, viruses) and the host immune system (e.g. innate immune molecules) is necessary for balancing health and disease outcomes within the host. These studies most often utilize vertebrate models; however, research in this field can benefit from diverse model systems that facilitate our ability to conduct experiments to identify phylogenically conserved rules influencing homeostasis in the gut of animals. The Dishaw has developed the use of a filter-feeding marine invertebrate chordate, Ciona robusta, to model such fundamental interactions[1]–[6]. While most biological diversity and functional contribution within microbiomes …

Atomistic Assessment Of Drug-Phospholipid Interactions Consequent To Cancer Treatment: A Study Of Anthracycline Cardiotoxicity, Yara Elsayed Ahmed

Theses and Dissertations

Despite being one of the most effective chemotherapeutic agents developed to date, Anthracyclines are notorious for their cardiotoxicity. Their clinical use is frequently limited both in dosage and in prescription due to the severe cardiac damage they cause. The mechanism of anthracycline-induced cardiotoxicity is not yet fully understood. However, it is hypothesized that interactions with the myocardial membrane play an important role in imparting cardiotoxicity. In this study, we use molecular dynamics simulations and density functional theory calculations to study the anthracycline drug molecules and the interactions that they have with the myocardial membrane. We construct a myocardial membrane model …