A5010729696- Lipid Membrane Structure and Behavior
- RNA Interference and Gene Delivery
- Axon Guidance and Neuronal Signaling
- Protein Structure and Dynamics
- Antifungal resistance and susceptibility
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- Antimicrobial Peptides and Activities
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- ATP Synthase and ATPases Research
- Nanoplatforms for cancer theranostics
- Ion channel regulation and function
- HIV Research and Treatment
- Hippo pathway signaling and YAP/TAZ
- Immune Cell Function and Interaction
- Enzyme Structure and Function
- Spectroscopy and Quantum Chemical Studies
- Chemical Synthesis and Analysis
- Fungal Infections and Studies
- Force Microscopy Techniques and Applications
- Computational Drug Discovery Methods
- HER2/EGFR in Cancer Research
- Cardiac electrophysiology and arrhythmias
- T-cell and B-cell Immunology
University of Tennessee at Knoxville
2016-2025
Yale University
2010-2019
Knoxville College
2018
University of New Haven
2011-2014
Institute of Molecular Biology and Biophysics
2009-2010
Universitat de Miguel Hernández d'Elx
2002-2010
University of Carabobo
2009
Centro de Investigaciones Biológicas Margarita Salas
2007-2009
Instituto de Biologia Molecular e Celular
2008
Utrecht University
2008
Significance Cholesterol regulates critical cell functions, including lysis, viral budding, and antibiotic resistance, by modifying the bending rigidity of membranes; i.e., ability membranes to bend or withstand mechanical stresses. A molecular-level understanding these functions requires knowledge how cholesterol modifies membrane mechanics over relevant length time scales. Currently, it is widely accepted that has no effect on properties unsaturated lipid membranes, implying viruses, for...
Abstract The practical application of nanoparticles (NPs) as chemotherapeutic drug delivery systems is often hampered by issues such poor circulation stability and targeting inefficiency. Here, we have utilized a simple approach to prepare biocompatible biodegradable pH-responsive hybrid NPs that overcome these issues. consist drug-loaded polylactic-co-glycolic acid (PLGA) core covalently ‘wrapped’ with crosslinked bovine serum albumin (BSA) shell designed minimize interactions proteins...
Photodynamic therapy (PDT) and photothermal (PTT) have gained considerable attention as potential alternatives to conventional cancer treatments. However, these approaches remain limited by low solubility, poor stability, inefficient targeting of many common photosensitizers (PSs) agents (PTAs). To overcome the aforementioned limitations, we engineered biocompatible biodegradable tumor-targeted upconversion nanospheres with imaging capabilities. The multifunctional consist a sodium yttrium...
The pHLIP peptide has three states: (I) soluble in aqueous buffer, (II) bound to the bilayer surface at neutral pH, and (III) inserted as a transmembrane (TM) helix acidic pH. membrane insertion of low pH can be used target tissues characteristic different diseases, such cancer. We find that α-helix content state II depends on lipid acyl chain length but not cholesterol, suggesting helicity may controlled by elastic bending modulus. Experiments with P20G variant show proline residue reduces...
Vulvovaginal candidiasis (VVC), caused primarily by the human fungal pathogen Candida albicans , results in significant quality-of-life issues for women worldwide. Candidalysin, a toxin derived from polypeptide (Ece1p) encoded ECE1 gene, plays crucial role driving immunopathology at vaginal mucosa. This study aimed to determine if expression and/or processing of Ece1p differs across C . isolates and whether this partly underlies differential pathogenicity observed clinically. Using targeted...
Several diseases, such as cancer, are characterized by acidification of the extracellular environment. Acidosis can be employed a target to specifically direct therapies diseased tissue. We have used first principles design an acidity-triggered rational membrane (ATRAM) peptide with high solubility in solution that is able interact lipid membranes pH-dependent fashion. Biophysical studies show ATRAM binds surface at pH 8.0. However, leads inserting into bilayer transmembrane α-helix. The...
Despite the prevalence of lipid transbilayer asymmetry in natural plasma membranes, most biomimetic model membranes studied are symmetric. Recent advances have helped to overcome difficulties preparing asymmetric liposomes vitro, allowing for examination a larger set relevant biophysical questions. Here, we investigate stability bilayers by measuring flip-flop with time-resolved small-angle neutron scattering (SANS). Asymmetric large unilamellar vesicles inner bilayer leaflets containing...
Candida albicans causes severe invasive candidiasis. C. infection requires the virulence factor candidalysin (CL) which damages target cell membranes. However, mechanism that CL uses to permeabilize membranes is unclear. We reveal forms membrane pores using a unique mechanism. Unexpectedly, readily assembled into polymers in solution. propose basic structural unit polymer formation oligomer, sequentially added string configuration can close loop. loops appear spontaneously insert become...
Different patterns of channel activity have been detected by patch clamping excised membrane patches from reconstituted giant liposomes containing purified KcsA, a potassium prokaryotes. The more frequent pattern has characteristic low opening probability and exhibits many other features reported for KcsA into planar lipid bilayers, including moderate voltage dependence, blockade Na(+), strict dependence on acidic pH opening. predominant gating event in this corresponds to the positive...
The α splice variant of p73 (p73α), a homologue the tumor suppressor p53, has close to its C terminus sterile motif (SAM), SAMp73, that is thought be involved in protein-protein interactions. Here, we report lipid binding properties this domain. Binding was assayed against zwitterionic (phosphatidylcholine) and anionic (phosphatidic acid) lipids studied by different biophysical techniques, namely, circular dichroism fluorescence spectroscopies differential scanning calorimetry. These...
We have used the pHlow insertion peptide (pHLIP) family to study role of aspartate embedding depth in pH-dependent transmembrane insertion. pHLIP binds surface a lipid bilayer as largely unstructured monomer at neutral pH. When pH is lowered, inserts spontaneously across membrane spanning α-helix. reversible when adjusted back value. One critical events facilitating protonation aspartates domain peptide: negative side chains these residues convert uncharged, polar forms, by altering...
Misregulation of the signaling axis formed by receptor tyrosine kinase (RTK) EphA2 and its ligand, ephrinA1, causes aberrant cell-cell contacts that contribute to metastasis. Solid tumors are characterized an acidic extracellular medium. We intend take advantage this tumor feature design new molecules specifically target tumors. created a novel pH-dependent transmembrane peptide, TYPE7, altering sequence domain EphA2. TYPE7 is highly soluble interacts with surface lipid membranes at neutral...
Photothermal therapy (PTT) has emerged as an effective cancer treatment strategy, which utilizes photothermal agents that accumulate at tumor sites and induce localized hyperthermia when irradiated. Near-infrared II (NIR II) fluorophores, such the polymethine cyanine-based dye IR1061, exhibit higher temporal resolution better tissue penetration, thereby making them promising candidates for PTT. However, challenges low water solubility in vivo short circulation times of these dyes limit their...
The receptor tyrosine kinase EphA2 drives cancer malignancy by facilitating metastasis. can be found in different self-assembly states: as a monomer, dimer, and oligomer. However, we have poor understanding regarding which state is responsible for driving pro-metastatic signaling. To address this limitation, developed SiMPull-POP, single-molecule method accurate quantification of membrane protein self-assembly. Our experiments reveal that reduction plasma cholesterol strongly promotes...
With the growing adoption of single-molecule fluorescence experiments, there is an increasing demand for efficient statistical methodologies and accurate analysis acquired measurements. Existing frameworks, such as those that use kinetic models, often rely on strong assumptions dynamics molecules fluorophores under study render them inappropriate general purpose step-counting applications, especially when systems exhibit uncharac-terized dynamics. Here, we propose a novel Bayesian...
Moderate concentrations of the alcohol 2,2,2-trifluoroethanol (TFE) cause coupled unfolding and dissociation into subunits homotetrameric potassium channel KcsA, in a process that is partially irreversible when protein solubilized plain dodecyl beta-d-maltoside (DDM) micelles [Barrera et al. (2005) Biochemistry 44, 14344-52]. Here we report transition from folded tetramer to unfolded monomer becomes completely reversible KcsA mixed composed detergent DDM lipids DOPE...