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Articles 1 - 13 of 13
Full-Text Articles in Biophysics
Painting Rich Six-Dimensional Pictures Using Polarized Fluorescence Microscopy, Matthew D. Lew
Painting Rich Six-Dimensional Pictures Using Polarized Fluorescence Microscopy, Matthew D. Lew
Electrical & Systems Engineering Publications and Presentations
No abstract provided.
Quantitative Approaches To Dissect Bivalent Antibody Binding And Detect Viruses From Aerosolized Samples, Ananya Benegal
Quantitative Approaches To Dissect Bivalent Antibody Binding And Detect Viruses From Aerosolized Samples, Ananya Benegal
McKelvey School of Engineering Graduate Student Theses & Dissertations
Influenza A virus (IAV) poses substantial epidemiological burdens around the world, with an estimated annual global mortality rate in the hundreds of thousands. Its rapid rate of mutation gives it a propensity for causing seasonal epidemics and occasional pandemics. As an airborne virus, IAV is most commonly transmitted through droplets and aerosols. Antibodies play a crucial role in the immune defense against IAV infection. By understanding the mechanisms of antibody-mediated defense and the transmission dynamics of IAV, we can better inform strategies for prevention, vaccination, and treatment, ultimately mitigating its impact on public health. The work encompassed in this dissertation …
Single-Molecule Orientation Imaging Reveals The Nano-Architecture Of Amyloid Fibrils Undergoing Growth And Decay, Brian Sun, Tianben Ding, Weiyan Zhou, Tara S. Porter, Matthew D. Lew
Single-Molecule Orientation Imaging Reveals The Nano-Architecture Of Amyloid Fibrils Undergoing Growth And Decay, Brian Sun, Tianben Ding, Weiyan Zhou, Tara S. Porter, Matthew D. Lew
Electrical & Systems Engineering Publications and Presentations
Amyloid-beta (Aβ42) aggregates are characteristic Alzheimer’s disease signatures, but probing how their nanoscale architectures influence their growth and decay remains challenging using current technologies. Here, we apply time-lapse single-molecule orientation-localization microscopy (SMOLM) to measure the orientations and rotational “wobble” of Nile blue (NB) molecules transiently binding to Aβ42 fibrils. We correlate fibril architectures measured by SMOLM with their growth and decay over the course of 5 to 20 min visualized by single-molecule localization microscopy (SMLM). We discover that stable Aβ42 fibrils tend to be well-ordered and signified by well-aligned NB orientations and small wobble. SMOLM also shows that increasing order …
The Mechanobiology Of Cell Plasticity, Yuan Hong
The Mechanobiology Of Cell Plasticity, Yuan Hong
McKelvey School of Engineering Graduate Student Theses & Dissertations
The cell is a sophisticated machine, integrating chemical and physical inputs to decide upon the mechanobiological outputs that the body requires every second, in cardiomyocytes that make heartbeats, in fibroblasts that heal wounds, and in sarcomeres that contract muscles. Malfunction of mechanotransduction or mechanical inputs is implicated in diseases such as fibrosis, cancers, and cardiomyopathies, and a pressing quest is underway to unravel the intricacies of how mechanical force orchestrates the activation of cells. This dissertation explores these fundamental mechanisms of cell activation using integrated mathematical and engineered cell culture models. The work begins with the discovery that the directionality …
Role Of Ligand Architecture On Collective Cell Invasion, Amrit Bagchi
Role Of Ligand Architecture On Collective Cell Invasion, Amrit Bagchi
McKelvey School of Engineering Graduate Student Theses & Dissertations
Epithelial cell collectives utilize extra-cellular matrix (ECM) fibers to undergo collective migration critical in regeneration, repair and cancer metastasis. However, very little is known about the various factors which determine the ability of cellular collectives to utilize ECM fibers to undergo these critical processes in-vivo. First part of the dissertation focusses on understanding how cell collectives exploit specific properties, like stiffness and fiber length to undergo collective streaming. It is also unclear how cellular forces, cell-cell adhesion, and velocities are coordinated within streams. To independently tune stiffness and collagen fiber length, we developed new hydrogels and discovered invasion-like streaming of …
Mechanisms Of Voltage-Gated Sodium Channel (Nav1.5) Regulation By Intracellular Fgfs, Paweorn Angsutararux
Mechanisms Of Voltage-Gated Sodium Channel (Nav1.5) Regulation By Intracellular Fgfs, Paweorn Angsutararux
McKelvey School of Engineering Graduate Student Theses & Dissertations
Voltage-gated sodium channels (NaV) conduct the inward current responsible for the initiation and propagation of the electrical signals in myocytes and neurons, known as action potentials (AP). Precise regulation of cardiac NaV1.5 opening and closing is essential for maintaining a normal heart beat. A disruption of NaV1.5 function, especially of its inactivation after opening, results in inherited cardiac arrhythmias such as Long QT Type 3 (LQT3) syndrome. This pathology is caused by an increase in the late INa that enters myocytes later in the AP and prolongs its duration. Late INa is also enhanced in acquired diseases such as heart …
Uncovering The Roles And Evolved Sequence Grammar Of Hypervariable Intrinsically Disordered Proteins In Bacterial Cell Division, Megan Cohan
McKelvey School of Engineering Graduate Student Theses & Dissertations
Across all domains of life, a defining hallmark of the onset of cell division is the formation of a cytokinetic ring at the center of the cell. Cell division is a tightly controlled process that involves various regulatory factors that modulate the assembly of the cytokinetic ring. In rod-shaped bacteria, the ring is termed the Z-ring after the protein FtsZ, which is foundational to ring formation and is the bacterial homolog of tubulin. Like tubulin, FtsZ is an assembling GTPase, where GTP binding promotes the cooperative assembly into FtsZ polymers that laterally associate to form bundles. While the GTPase domain …
Single‐Molecule 3d Orientation Imaging Reveals Nanoscale Compositional Heterogeneity In Lipid Membranes, Jin Lu, Hesam Mazidi, Tianben Ding, Oumeng Zhang, Matthew D. Lew
Single‐Molecule 3d Orientation Imaging Reveals Nanoscale Compositional Heterogeneity In Lipid Membranes, Jin Lu, Hesam Mazidi, Tianben Ding, Oumeng Zhang, Matthew D. Lew
Electrical & Systems Engineering Publications and Presentations
In soft matter, thermal energy causes molecules to continuously translate and rotate, even in crowded environments, thereby impacting the spatial organization and function of most molecular assemblies, such as lipid membranes. Directly measuring the orientation and spatial organization of large collections (>3000 molecules μm−2) of single molecules with nanoscale resolution remains elusive. In this paper, we utilize SMOLM, single‐molecule orientation localization microscopy, to directly measure the orientation spectra (3D orientation plus “wobble”) of lipophilic probes transiently bound to lipid membranes, revealing that Nile red's (NR) orientation spectra are extremely sensitive to membrane chemical composition. SMOLM images resolve …
Convex Relaxations For Particle-Gradient Flow With Applications In Super-Resolution Single-Molecule Localization Microscopy, Hesam Mazidisharfabadi
Convex Relaxations For Particle-Gradient Flow With Applications In Super-Resolution Single-Molecule Localization Microscopy, Hesam Mazidisharfabadi
McKelvey School of Engineering Graduate Student Theses & Dissertations
Single-molecule localization microscopy (SMLM) techniques have become advanced bioanalytical tools by quantifying the positions and orientations of molecules in space and time at the nanoscale. With the noisy and heterogeneous nature of SMLM datasets in mind, we discuss leveraging particle-gradient flow 1) for quantifying the accuracy of localization algorithms with and without ground truth and 2) as a basis for novel, model-driven localization algorithms with empirically robust performance. Using experimental data, we demonstrate that overlapping images of molecules, a typical consequence of densely packed biological structures, cause biases in position estimates and reconstruction artifacts. To minimize such biases, we develop …
Brain-Computer Interfaces Using Electrocorticography And Surface Stimulation, Jesse Wheeler
Brain-Computer Interfaces Using Electrocorticography And Surface Stimulation, Jesse Wheeler
McKelvey School of Engineering Graduate Student Theses & Dissertations
The brain connects to, modulates, and receives information from every organ in the body. As such, brain-computer interfaces (BCIs) have vast potential for diagnostics, medical therapies, and even augmentation or enhancement of normal functions. BCIs provide a means to explore the furthest corners of what it means to think, to feel, and to act—to experience the world and to be who you are. This work focuses on the development of a chronic bi-directional BCI for sensorimotor restoration through the use of separable frequency bands for recording motor intent and providing sensory feedback via electrocortical stimulation. Epidural cortical surface electrodes are …
Pharmacology Of Organic Cation Transporters: Focus On Structure-Function Relationships In Oct3 (Slc22a3), Dan C. Li
Undergraduate Theses—Unrestricted
Organic Cation Transporters (OCTs) are polyspecific, facilitative transporters that play major roles in metabolite and drug clearance. OCTs are promising drug targets and elucidating their mechanisms of substrate recognition is crucial for rational drug design. OCT-mediated transport of polyvalent cations remains unexplored. OCT-expressing Xenopus laevis oocytes were used to assess transport of polyamines, ubiquitous polyvalent cations of broad physiological import, but for which transport mechanisms are unknown. Dose-response analysis of radiolabelled substrate uptake revealed that polyamines are relatively low affinity, but high turnover substrates for OCTs compared to model substrate methyl-4-phenylpyridinium (MPP+). Polyamine analogs of varying hydrophobic character …
A Force Of Nature: Molecular Mechanisms Of Mechanoperception In Plants, Gabriele B. Monshausen, Elizabeth S. Haswell
A Force Of Nature: Molecular Mechanisms Of Mechanoperception In Plants, Gabriele B. Monshausen, Elizabeth S. Haswell
Biology Faculty Research
The ability to sense and respond to a wide variety of mechanical stimuli-gravity, touch, osmotic pressure, or the resistance of the cell wall-is a critical feature of every plant cell, whether or not it is specialized for mechanotransduction. Mechanoperceptive events are an essential part of plant life, required for normal growth and development at the cell, tissue, and whole-plant level and for the proper response to an array of biotic and abiotic stresses. One current challenge for plant mechanobiologists is to link these physiological responses to specific mechanoreceptors and signal transduction pathways. Here, we describe recent progress in the identification …
Single-Molecule Analysis Of The Microtubule Cross-Linking Protein Map65-1 Reveals A Molecular Mechanism For Contact-Angle-Dependent Microtubule Bundling, Amanda Tulin, Sheri Mcclerklin, Yue Huang, Ram Dixit
Single-Molecule Analysis Of The Microtubule Cross-Linking Protein Map65-1 Reveals A Molecular Mechanism For Contact-Angle-Dependent Microtubule Bundling, Amanda Tulin, Sheri Mcclerklin, Yue Huang, Ram Dixit
Biology Faculty Research
Bundling of microtubules (MTs) is critical for the formation of complex MT arrays. In land plants, the interphase cortical MTs form bundles specifically following shallow-angle encounters between them. To investigate how cells select particular MT contact angles for bundling, we used an in vitro reconstitution approach consisting of dynamic MTs and the MT-cross-linking protein MAP65-1. We found that MAP65-1 binds to MTs as monomers and inherently targets antiparallel MTs for bundling. Dwell-time analysis showed that the affinity of MAP65-1 for antiparallel overlapping MTs is about three times higher than its affinity for single MTs and parallel overlapping MTs. We also …