Biophysics Commons^™

Screening Of Human Serum/Plasma Using Vibrational Spectroscopy For Early Disease Diagnostics And Therapeutic Drug Monitoring, Drishya Rajan Parachalil [Thesis]

Doctoral

Analysis of analytes present in the blood stream can potentially deliver crucial information on patient health and indicate the presence of numerous pathologies. Existing clinical techniques for this analysis can, however, be costly and time-consuming. The potential of Raman spectroscopic analysis of human plasma and/or serum for diagnostic purposes has been widely investigated and, increasingly, its feasibility for clinical translation has been explored. However, as the concentration of many analytes in plasma/serum is relatively low, to date such analysis has commonly been performed on air-dried drops deposited on substrates, leading to inhomogeneity and inconsistencies. This study explores the potential of …

Computational Study Of Disease Related Proteins Form Electrostatic Point Of View, Chitra Bahadur Karki

Open Access Theses & Dissertations

In the last three decades, many giant DNA viruses have been discovered. The giant viruses present a unique and essential research frontier for the study of self-assembly and regulation of supramolecular assemblies. The question on how these giant DNA viruses assemble thousands of proteins so accurately to form their protein shell, the capsids, remains largely unanswered. Revealing the mechanisms of giant virus assembly will help to discover the mysteries of many self-assembly biology problems. Paramecium Bursaria Chlorella Virus 1 (PBCV-1) is one of the most intensively studied giant viruses. Based on the high-resolution structure of PBCV-1, we implemented a multi-scale …

Novel Methods For The Inactivation Of Cruzain For The Prevention And Treatment Of Chagas Disease, Veronica Gonzalez

Open Access Theses & Dissertations

Chagas Disease, also known as American Trypanosomiasis, is endemic to Latin American and is gradually making its way to other countries. The disease is caused by Trypanosoma cruzi, a protozoan parasite that causes lesions and inflammation of organs including the heart, esophagus, and colon. Over 30% of people infected will develop heart disease which can be fatal if untreated. While no vaccine is yet available, research is currently being conducted in finding new treatments for the disease. One target is an enzyme that is believed to help the progression of the disease. Cruzain, a cysteine protease expressed as a pro-enzyme, …

Non Linear Optics For Materials Fabrication And Medical Instrumentation, Aurelio Paez

Open Access Theses & Dissertations

Two-photon absorption is a nonlinear optical process where two photons are absorbed by a molecule simultaneously. The probability of this quantum phenomenon is proportional to the quadratic excitation of light intensity. It has many applications in biomedical and materials research, such as two-photon fluorescence microcopy. The first project is to apply two-photon absorption induced bond cleavage in photoreactive materials for engineering 3D tissue scaffolds. The major challenge for growing thick 3D tissues is the lack of vasculature, where nutrients and oxygen can be delivered to the growing cells. Our collaborators have synthesized a novel polypeptide that is composed of 34-mer …

Non-Contact Trapping And Stretching Of Biological Cells Using Dual-Beam Optical Stretcher On Microfluidic Platform, Aotuo Dong, Balaadithya Uppalapati, Shariful Islam, Brandon Gibbs, Ganesan Kamatchi, Sacharia Albin, Makarand Deo

Electrical & Computer Engineering Faculty Publications

Optical stretcher is a tool in which two counter-propagating, slightly diverging, and identical laser beams are used to trap and axially stretch microparticles in the path of light. In this work, we utilized the dual-beam optical stretcher setup to trap and stretch human embryonic kidney (HEK) cells and mammalian breast cancer (MBC) cells. Experiments were performed by exposing the HEK cells to counter-propagating laser beams for 30 seconds at powers ranging from 100 mW to 561 mW. It was observed that the percentage of cell deformation increased from 16.7% at 100 mW to 40.5% at 561 mW optical power. The …

The Effect Of Styrene-Maleic Acid (Sma) Copolymers On Solubilizing Lipid Bilayers And Forming Nanodiscs, Ghada Alramadan

Dissertations and Theses

Cell membranes, or plasma membranes, play an essential role in the structure and the function of living cells. In 1972, the fluid mosaic membrane model was the first unifying paradigm of membrane structure. It is no longer considered adequate because evidence of many non-homogeneous lipid structures in both natural and model membranes have been discovered over the past thirty years. The field of membrane biophysics now uses updated versions of the mosaic model, which consists of the complex mixture of different lipid species. The lipid species found in natural membranes produce a range of dynamic, laterally segregated, non-homogeneous domains, which …

Optimization Of Detergent-Mediated Reconstitution Of Influenza A M2 Protein Into Proteoliposomes, Catherine Hirshfeld Crouch, Margaret H. Bost , '17, Tae H. Kim , '14, Bryan M. Green , '16, Douglas Stuart Arbuckle , '17, Carl H. Grossman, Kathleen P. Howard

Physics & Astronomy Faculty Works

We report the optimization of detergent-mediated reconstitution of an integral membrane-bound protein, full-length influenza M2 protein, by direct insertion into detergent-saturated liposomes. Detergent-mediated reconstitution is an important method for preparing proteoliposomes for studying membrane proteins, and must be optimized for each combination of protein and membrane constituents used. The purpose of the reconstitution was to prepare samples for site-directed spin-labeling electron paramagnetic resonance (SDSL-EPR) studies. Our goals in optimizing the protocol were to minimize the amount of detergent used, reduce overall proteoliposome preparation time, and confirm the removal of all detergent. The liposomes were comprised of (1-palmitoyl-2-oleyl-sn-glycero-phosphocholine (POPC) and 1-palmitoyl-2-oleyl-sn-glycero-3-[phospho-rac-(1-glycerol)] …

Data On Spectrum-Based Fluorescence Resonance Energy Transfer Measurement Of E. Coli Multidrug Transporter Acrb, Yuguang Cai, Thomas E. Wilkop, Yinan Wei

Chemistry Faculty Publications

This paper presented the dataset of correction parameters used in the determination of the energy transfer efficiencies from the spectrum-based fluorescence resonance energy transfer (FRET) measurement in a trimeric membrane protein AcrB. The cyan fluorescent protein (CFP) and yellow fluorescent protein (YPet) were used as the donor and acceptor, respectively. Two AcrB fusion proteins were constructed, AcrB-CFP and AcrB-YPet. The proteins were co-expressed in Escherichia coli cells, and energy transfer efficiency were determined in live cells. To obtain reliable energy transfer data, a complete set of correction parameters need to be first determined to accommodate for factors such as background …

Harnessing The Physical Properties Of Zno Nanoparticles For Biological Applications And Factors That Impact Zno Nanoparticle Toxicity, Joshua Eixenberger

Boise State University Theses and Dissertations

The production of materials at the nanoscale leads to novel properties and has made the field of nanotechnology a part of everyday life. Numerous applications of nanomaterials have led to their use in electronics, optics, and medicine. However, creating materials at such a small size brings them on the same scale as many biomolecules and cellular components, altering their interactions with biological systems. This can lead to unintended biological impacts as many nanomaterials are considerably more toxic than their bulk counterpart material. ZnO nanoparticles (nZnO) are particularly interesting in this context. The FDA classifies ZnO as a generally recognized as …

Metformin, Oxidative Stress, And Infertility: A Way Forward, Rehana Rehman, Syed Hani Abidi, Faiza Alam

Department of Biological & Biomedical Sciences

No abstract provided.

Combined High-Speed Single Particle Tracking Of Membrane Proteins And Super-Resolution Of Membrane-Associated Structures, Hanieh Mazloom Farsibaf, Keith A. Lidke

Shared Knowledge Conference

Many experiments have shown that the diffusive motion of lipids and membrane proteins are slower on the cell surface than those in artificial lipid bilayers or blebs. One hypothesis that may partially explain this mystery is the effect of the cytoskeleton structures on the protein dynamics. A model proposed by Kusumi [1] is the Fence-Picket Model which describes the cell membrane as a set of compartment regions, each ~ 10 to 200 nm in size, created by direct or indirect interaction of lipids and proteins with actin filaments just below the membrane. To test this hypothesis, we have assembled a …

Accurate Flexible Refinement Of Atomic Models Against Medium-Resolution Cryo-Em Maps Using Damped Dynamics, Julio A. Kovacs, Vitold E. Galkin, Willy Wriggers

Mechanical & Aerospace Engineering Faculty Publications

Background: Dramatic progress has recently been made in cryo-electron microscopy technologies, which now make possible the reconstruction of a growing number of biomolecular structures to near-atomic resolution. However, the need persists for fitting and refinement approaches that address those cases that require modeling assistance.

Methods: In this paper, we describe algorithms to optimize the performance of such medium-resolution refinement methods. These algorithms aim to automatically optimize the parameters that define the density shape of the flexibly fitted model, as well as the time-dependent damper cutoff distance. Atomic distance constraints can be prescribed for cases where extra containment of parts of …

Towards An Atomic Level Model Of The Structure And Calmodulin Mediated Activation Of Eef-2k, Nathan E. Will

Dissertations, Theses, and Capstone Projects

Eukaryotic elongation factor 2 kinase (eEF-2K), the only calmodulin (CaM) dependent member of the a-kinase, phosphorylates eukaryotic elongation factor 2 (eEF-2) on a specific residue (Thr-56), decreasing its affinity for the ribosome and reducing the rate of peptide chain elongation during protein translation. In contrast to the “release-of-inhibition’ mechanism operative in most CaM-dependent proteins kinases, the activation of eEF-2K is proposed to occur through a two-step process subsequent to the engagement of CaM and involves (1) auto-phosphorylation on T348 and (2) engagement of an allosteric site by phospho-T348 leading to a state with the highest activity towards the substrate eEF-2. …

Supercharged Models Of Intrinsically Disordered Proteins And Their Utility In Sensing, Peter J. Schnatz

Dissertations, Theses, and Capstone Projects

In this thesis I show that greatly increasing the magnitude of a protein’s net charge using surface supercharging transforms that protein into a ligand-gated or counterion-gated conformational molecular switch. To demonstrate this I first modified the designed helical bundle hemoprotein H4 using simple molecular modeling, creating a highly charged protein which both unfolds reversibly at low ionic strength and undergoes the ligand-induced folding transition commonly observed in signal transduction by intrinsically disordered proteins in biology. Due to the high surface charge density, ligand binding to this protein is allosterically activated by low concentrations of divalent cations and the polyamine spermine. …

A Hybrid Lagrangian–Eulerian Particle Model For Ecosystem Simulation, Pengfei Xue, David J. Schwab, Xing Zhou, Chenfu Huang, Ryan Kibler, Xinyu Ye

Michigan Tech Publications, Part 1

Current numerical methods for simulating biophysical processes in aquatic environments are typically constructed in a grid-based Eulerian framework or as an individual-based model in a particle-based Lagrangian framework. Often, the biogeochemical processes and physical (hydrodynamic) processes occur at different time and space scales, and changes in biological processes do not affect the hydrodynamic conditions. Therefore, it is possible to develop an alternative strategy to grid-based approaches for linking hydrodynamic and biogeochemical models that can significantly improve computational efficiency for this type of linked biophysical model. In this work, we utilize a new technique that links hydrodynamic effects and biological processes …

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 …

Structure And Thermodynamics Of Polyglutamine Peptides And Amyloid Fibrils Via Metadynamics And Molecular Dynamics Simulations, Riley Workman

Electronic Theses and Dissertations

Aggregation of polyglutamine (polyQ)-rich polypeptides in neurons is a marker for nine neurodegenerative diseases. The molecular process responsible for the formation of polyQ fibrils is not well understood and represents a growing area of study. To enable development of treatments that could interfere with aggregation of polyQ peptides, it is crucial to understand the molecular mechanisms by which polyQ peptides aggregate into fibrils. Many experimental techniques have been employed to probe polyQ aggregation, however, observations from these studies have not lead to a unified understanding of the properties of these systems, instead yielding competing, fragmented theories of polyQ aggregation. This …

Gq Noncanonical Roles In Translational Regulation, Brett Demarco

Electronic Theses and Dissertations

This study investigates protein nucleic acid interactions, focusing on G-quadruplex (GQ) forming DNA/RNA in human disease. GQ structures are formed in DNA/RNA, when four guanine residues form planar tetrads stabilized by Hoogsteen base pairing, that stack forming a GQ structure stabilized by potassium ions. These GQ structures are targeted by the arginine glycine-glycine (RGG) RNA-binding domain. Fragile X mental retardation protein (FMRP), a translation regulator protein implicated in the fragile X syndrome, has an RGG domain and has been previously shown to interact with neuronal GQ forming messenger RNA (mRNA). We have investigated three neuronal FMRP mRNA targets that we …

Characterization Of A Variant Of Tuberous Sclerosis Complex 2 And Its Interaction With Rheb, Sowmya Sivakumar

Graduate Theses and Dissertations

Protein-protein interactions are vital in maintaining proper function and homeostasis in cells. Some signaling pathways are regulated by G-proteins that work like switches to activate and deactivate pathways. Mutations in these proteins, their effectors or the interaction between proteins may cause dysregulation of signals that can lead to many diseases.

Rheb, Ras homology enriched in brain, is a Ras family GTPase that is vital in regulation of the mTOR (mammalian target of rapamycin) pathway that signals cell proliferation and growth. Due to the low intrinsic GTPase activity of Rheb, a GTPase activating protein (GAP), Tuberous Sclerosis Complex 2 (TSC2) down …

Cause Of Cambrian Explosion - Terrestrial Or Cosmic?, Edward J. Steele, Shirwan Al-Mufti, Kenneth A. Augustyn, Rohana Chandrajith, John P. Coghlan, S. G. Coulson, Et. Al.

Michigan Tech Publications, Part 1

We review the salient evidence consistent with or predicted by the Hoyle-Wickramasinghe (H-W) thesis of Cometary (Cosmic) Biology. Much of this physical and biological evidence is multifactorial. One particular focus are the recent studies which date the emergence of the complex retroviruses of vertebrate lines at or just before the Cambrian Explosion of ∼500 Ma. Such viruses are known to be plausibly associated with major evolutionary genomic processes. We believe this coincidence is not fortuitous but is consistent with a key prediction of H-W theory whereby major extinction-diversification evolutionary boundaries coincide with virus-bearing cometary-bolide bombardment events. A second focus is …