Physics Commons^™

Quantifying Anticancer Drug Doxorubicin Binding To Dna Using Optical Tweezers, Zachary Ells

Honors Program Theses and Projects

Doxorubicin is a successful anticancer drug approved for use in the 1970s and is considered to be one of the most effective cancer treatment methods today. Although Doxorubicin has positive survival statistics it has very negative side effects in many cases. Bleeding from the soles of the palms and feet, along with excruciating pain is often exhibited through the administration of this drug. Based on the preliminary findings utilizing optical tweezers we anticipate that this study will provide critical information about the drug binding mechanism. Single molecule biophysics techniques have provided useful insight into the DNA-binding mechanisms of small molecules. …

Controlled Membrane Remodeling By Nanospheres And Nanorods: Experiments Targeting The Design Principles For Membrane-Based Materials, Sarah Zuraw-Weston

Doctoral Dissertations

In this thesis we explore two experimental systems probing the interactions of nanoparticles with lipid bilayer membranes. Inspired by the ability of cell membranes to alter their shape in response to bound particles, we report two experimental studies: one of nanospheres the other of long, slender nano-rods binding to lipid bilayer vesicles and altering the membrane shape. Our work illuminates the role of particle geometry, particle concentration, adhesion strength and membrane tension in how membrane morphology is determined. We combine giant unilamellar vesicles with oppositely charged nanoparticles, carefully tuning adhesion strength, membrane tension and particle concentration. In the case of …

Live Cell Super-Resolution Microscopy Quanitifies An Interaction Between Influenza Hemagglutinin And Phosphatidylinositol 4,5-Bisphosphate, Jaqulin N. Wallace

Electronic Theses and Dissertations

Influenza virus, colloquially known as the flu, is an acute respiratory disease that infects several millions of individuals each year in the U.S. and kills tens of thousands of those infected. Yearly viral vaccines are widely available, however, due to the virus’s high mutation rate, their efficacy varies greatly. Due to the variability in vaccine efficiency against seasonal influenza, and the potential for even more pathogenic versions of influenza to emerge at any time, there is a high demand for a universal treatment option.

Influenza virus hijacks a variety of host cell components in order to replicate. The glycoprotein hemagglutinin …

Probing Structure, Function And Dynamics In Bacterial Primary And Secondary Transporter-Associated Binding Proteins, Shantanu Shukla

Doctoral Dissertations

Substrate binding proteins (SBPs) are ubiquitous in all life forms and have evolved to perform diverse physiological functions, such as in membrane transport, gene regulation, neurotransmission, and quorum sensing. It is quite astounding to observe such functional diversity among the SBPs even when they are restricted by their fold space. Therefore, the SBPs are an excellent set of proteins that can reveal how proteins evolution novel function in a structurally conserved/constrained fold. This study attempts to understand the phenomenon of affinity and specificity evolution in SBPs by combining a set of biochemical, biophysical, and structural studies on the SBPs involved …

Using Second Harmonic Generation To Study Gram-Positive Bacterial Membranes, Lindsey N. Miller

Doctoral Dissertations

Understanding how small-molecules, such as drugs, interact with bacterial membranes can quickly unravel into much more perplexing questions. No two bacterial species are alike, especially when comparing their membrane compositions which can even be altered by incorporating fatty acids from their surrounding environment into their lipid-membrane composition. To further complicate the comparison, discrete alterations in small-molecule structures can result in vastly different membrane-interaction outcomes, giving rise to the need for more "label-free" studies when analyzing drug mechanisms. The work presented in this dissertation highlights the benefits to using nonlinear spectroscopy and microscopy techniques for probing small-molecule interactions in living bacteria. …

Macromolecular Structure Determination At X-Ray Free Electron Lasers From Single-Particle Imaging To Time-Resolved X-Ray Crystallography, Ishwor Poudyal

Theses and Dissertations

X-ray free-electron lasers (XFELs) open the possibility of obtaining diffraction information from a single biological macromolecule. This is because XFELs can generate extremely intense X-ray pulses which are so short that diffraction data can be collected before the sample is destroyed. By collecting a sufficient number of single-particle diffraction patterns from many tilts of a molecule relative to the X-ray beam, the three-dimensional electron density can be reconstructed ab-initio. The resolution and therefore the information content of the data will ultimately depend largely on the number of patterns collected at the experiment. We estimate the number of diffraction patterns required …

Mathematical Modelling Of Temperature Effects On The Afd Neuron Of Caenorhabditis Elegans, Zachary Mobille, Rosangela Follmann, Epaminondas Rosa

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

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 …

Pressure Driven Desalination Utilizing Nanomaterials, Fangyou Xie

Master's Theses

Nanomaterials such as graphene oxide and carbon nanotubes, have demonstrated excellent properties for membrane desalination, including decrease of maintenance, increase of flux rate, simple solution casting, and impressive chemical inertness. Here, two projects are studied to investigate nanocarbon based membrane desalination. The first project is to prepare hybrid membranes with amyloid fibrils intercalated with graphene oxide sheets. The addition of protein amyloid fibrils expands the interlayer spacing between graphene oxide nanosheets and introduces additional functional groups in the diffusion pathways, resulting in increase of flux rate and rejection rate for the organic dyes. Amyloid fibrils also provide structural assistance to …

Specificity Of Ssb Binding To Its Interacting Proteins And Multiple Allosteric Effects Of Ssb C-Terminal Tail On Assembly And Dna Binding Of E. Coli Recor Proteins, Min Kyung Shinn

Arts & Sciences Electronic Theses and Dissertations

The homo-tetrameric E. coli single strand (ss) DNA binding (SSB) protein is an essential component in DNA maintenance for its role in binding and protecting single stranded DNA intermediates via its N-terminal DNA binding domain (DBD). SSB also acts as a hub to recruit at least 17 SSB interacting proteins (SIPs) involved in DNA replication, recombination, and repair via its 9 amino acid C-terminal acidic tip region. A 56 amino acid intrinsically disordered linker connects the DBD and the acidic tip and plays a role in cooperative binding to ssDNA. Using isothermal titration calorimetry, I determined that the SSB-Ct peptides …

Snow-Albedo Feedback In Northern Alaska: How Vegetation Influences Snowmelt, Lucas C. Reckhaus

Theses and Dissertations

This paper investigates how the snow-albedo feedback mechanism of the arctic is changing in response to rising climate temperatures. Specifically, the interplay of vegetation and snowmelt, and how these two variables can be correlated. This has the potential to refine climate modelling of the spring transition season. Research was conducted at the ecoregion scale in northern Alaska from 2000 to 2020. Each ecoregion is defined by distinct topographic and ecological conditions, allowing for meaningful contrast between the patterns of spring albedo transition across surface conditions and vegetation types. The five most northerly ecoregions of Alaska are chosen as they encompass …

Evolutionary Algorithms Converge Towards Evolved Biological Photonic Structures, Mamadou Aliou Barry, Vincent Berthier, Bobo D. Wilts, Marie-Claire Cambourieux, Pauline Bennet, Rémi Pollès, Olivier Teytaud, Emmanuel Centeno, Nicolas Biais, Antoine Moreau

Publications and Research

Nature features a plethora of extraordinary photonic architectures that have been optimized through natural evolution in order to more efciently refect, absorb or scatter light. While numerical optimization is increasingly and successfully used in photonics, it has yet to replicate any of these complex naturally occurring structures. Using evolutionary algorithms inspired by natural evolution and performing particular optimizations (maximize refection for a given wavelength, for a broad range of wavelength or maximize the scattering of light), we have retrieved the most stereotypical natural photonic structures. Whether those structures are Bragg mirrors, chirped dielectric mirrors or the gratings on top of …

Phenotypic Switching Of Bacterial Cells In Extreme Environments, Sudip Nepal

Graduate Theses and Dissertations

A large number of terrestrial microbial lives thrive in extremes of environmental conditions, including extremes of pressure, temperature, salinity, pH, and a combination of them. For example, all the marine biomass thrive at high hydrostatic pressure depending on depth. The temperature in the ocean can be very high near the hydrothermal vents and salinity and pH depends on the composition of salt in the surrounding areas. On the surface, hot springs, lakes and geysers provide high temperature conditions, while many places are permafrost regions with subzero temperatures. There is an emerging body of work on the viability, genomics, and metagenomics …

Circuits With Broken Fibration Symmetries Perform Core Logic Computations In Biological Networks, Ian Leifer, Flaviano Morone, Saulo D. S. Reis, José S. Andrade Jr., Mariano Sigman, Hernán A. Makse

Publications and Research

We show that logic computational circuits in gene regulatory networks arise from a fibration symmetry breaking in the network structure. From this idea we implement a constructive procedure that reveals a hierarchy of genetic circuits, ubiquitous across species, that are surprising analogues to the emblematic circuits of solid-state electronics: starting from the transistor and progressing to ring oscillators, current-mirror circuits to toggle switches and flip-flops. These canonical variants serve fundamental operations of synchronization and clocks (in their symmetric states) and memory storage (in their broken symmetry states). These conclusions introduce a theoretically principled strategy to search for computational building blocks …

Kinetic Exclusion Assay Of Biomolecules By Aptamer Capture, Mark H. Smith, Daniel Fologea

Physics Faculty Publications and Presentations

DNA aptamers are short nucleotide oligomers selected to bind a target ligand with affinity and specificity rivaling that of antibodies. These remarkable features recommend aptamers as candidates for analytical and therapeutic applications that traditionally use antibodies as biorecognition elements. Numerous traditional and emerging analytical techniques have been proposed and successfully implemented to utilize aptamers for sensing purposes. In this work, we exploited the analytical capabilities offered by the kinetic exclusion assay technology to measure the affinity of fluorescent aptamers for their thrombin target and quantify the concentration of analyte in solution. Standard binding curves constructed by using equilibrated mixtures of …

Proton Pumping Mechanism In Cytochrome C Oxidase, Xiuhong Cai

Dissertations, Theses, and Capstone Projects

Cytochrome c Oxidase (CcO), is the terminal electron acceptor in the membrane bound aerobic respiratory chain. It reduces O₂ to water. The energy released by this reaction is stored by pumping protons from the high pH, N-side of the membrane to the low pH, P-side. The generated proton gradient provides the motive force for synthesis of ATP by the ATP synthase.

Building a proton gradient across the membrane requires that proton transport must occur along controllable proton pathways to prevent proton leakage to the N-side. It has been suggested that CcO function requires proton transfer channels in both the …

Modeling Single Microtubules As A Colloidal System To Measure The Harmonic Interactions Between Tubulin Dimers In Bovine Brain Derived Versus Cancer Cell Derived Microtubules, Arooj Aslam

Dissertations

The local properties of tubulin dimers dictate the properties of the larger microtubule assembly. In order to elucidate this connection, tubulin-tubulin interactions are be modeled as harmonic interactions to map the stiffness matrix along the length of the microtubule. The strength of the interactions are measured by imaging and tracking the movement of segments along the microtubule over time, and then performing a fourier transform to extract the natural vibrational frequencies. Using this method the first ever reported experimental phonon spectrum of the microtubule is reported. This method can also be applied to other biological materials, and opens new doors …

Additive Modulation Of Dna-Dna Interactions By Interstitial Ions, Wei Meng, Raju Timsina, Abby Bull, Kurt Andresen, Xiangyun Qiu

Physics and Astronomy Faculty Publications

Quantitative understanding of biomolecular electrostatics, particularly involving multivalent ions and highly charged surfaces, remains lacking. Ion-modulated interactions between nucleic acids provide a model system in which electrostatics plays a dominant role. Using ordered DNA arrays neutralized by spherical cobalt3+ hexammine and Mg2+ ions, we investigate how the interstitial ions modulate DNA-DNA interactions. Using methods of ion counting, osmotic stress, and x-ray diffraction, we systematically determine thermodynamic quantities, including ion chemical potentials, ion partition, DNA osmotic pressure and force, and DNA-DNA spacing. Analyses of the multidimensional data provide quantitative insights into their interdependencies. The key finding of this study is that …

Phantoms To Placentas: Mr Methods For Oxygen Quantification, Kelsey Meinerz

Arts & Sciences Electronic Theses and Dissertations

Molecular oxygen (O2) is vital for efficient energy production and improper oxygenation is a hallmark of disease or metabolic dysfunction. In many pathologies, knowledge of tissue oxygen levels (pO2) could aid in diagnosis and treatment planning. The gold standard for pO2 measures in tissue are implantable probes, which are invasive, require surgery for placement, and are inaccessible to certain regions of the body. Methods for determining pO2 both non-invasively and quantitatively are lacking. The slight paramagnetic nature of O2 provides opportunities to non-invasively characterize pO2 in tissue via magnetic resonance (MR) techniques. As such, O2 can be treated as a …

Molecular Insights Into Microbial Adhesion, Roger Davies Klein

Arts & Sciences Electronic Theses and Dissertations

Antibiotic-resistant bacterial infections are a serious and immediate threat to global public health. In the United States alone, over 2 million individuals develop antibiotic-resistant infections annually, resulting in 23,000 deaths and $20 billion in excess health care costs. Virulence factors that allow bacteria to invade and persist within the host are promising targets for novel antimicrobial agents that could be used to curb the spread of antibiotic resistance. Development of therapeutics that can selectively eliminate pathogenic bacteria while sparing the beneficial host microbiota requires a detailed molecular understanding of critical virulence factors that facilitate interactions between pathogens and their environments. …

Investigatin Actin-Myosin Mechanics To Model Heart Disease Using Fluorescence Microscopy And Optical Trapping, Justin Edward Reynolds

Honors Theses

Hypertrophic cardiomyopathy (HCM) is a hereditary disease in which the myocardium becomes hypertrophied, making it more difficult for the heart to pump blood. HCM is commonly caused by a mutation in the β-cardiac myosin II heavy chain. Myosin is a motor protein that facilitates muscle contraction by converting chemical energy from ATP hydrolysis into mechanical work and concomitantly moving along actin filaments. Optical tweezers have been used previously to analyze single myosin biophysical properties; however, myosin does not work as a single unit within the heart. Multiple myosin interacts to displace actin filaments and do not have the same properties …

Temporary Membrane Permeabilization Via The Pore-Forming Toxin Lysenin, Nisha Shrestha, Christopher A. Thomas, Devon Richtsmeier, Andrew Bogard, Rebecca Hermann, Malyk Walker, Gamid Abatchev, Raquel J. Brown, Daniel Fologea

Physics Faculty Publications and Presentations

Pore-forming toxins are alluring tools for delivering biologically-active, impermeable cargoes to intracellular environments by introducing large conductance pathways into cell membranes. However, the lack of regulation often leads to the dissipation of electrical and chemical gradients, which might significantly affect the viability of cells under scrutiny. To mitigate these problems, we explored the use of lysenin channels to reversibly control the barrier function of natural and artificial lipid membrane systems by controlling the lysenin’s transport properties. We employed artificial membranes and electrophysiology measurements in order to identify the influence of labels and media on the lysenin channel’s conductance. Two cell …

Quantification Of Interactions Between Influenza Hemagglutinin And Host Cell Phosphoinositides By Super-Resolution Microscopy, Matthew T. Parent

Electronic Theses and Dissertations

The influenza viral membrane protein hemagglutinin (HA) forms dense nanoscale clusters on host cell plasma membranes (PM), but the mechanisms that direct HA clustering are not well understood. Previous studies have observed HA associated with actin rich regions of the PM, but there are no known direct interactions between HA and actin. Phosphatidylinositol 4,5-biphosphate (PIP2) is a signaling lipid in the PM which can regulate the actin cytoskeleton, and actin comets initiated by PIP2 are known to be exploited by HA to reach the PM of infected cells. PIP2 is also used by other viruses, such as HIV and Ebola, …

Got Science? Club, Nora Husein, Randa Ismail

Honors Expanded Learning Clubs

Got Science? Club allows students to learn about the science that can be found in our daily lives using everyday items such as food and school supplies. Students will learn about these sciences through hands-on experiments, allowing them to truly experience the science around them.

Fibration Symmetries Uncover The Building Blocks Of Biological Networks, Flaviano Morone, Ian Leifer, Hernán A. Makse

Publications and Research

A major ambition of systems science is to uncover the building blocks of any biological network to decipher how cellular function emerges from their interactions. Here, we introduce a graph representation of the information flow in these networks as a set of input trees, one for each node, which contains all pathways along which information can be transmitted in the network. In this representation, we find remarkable symmetries in the input trees that deconstruct the network into functional building blocks called fibers. Nodes in a fiber have isomorphic input trees and thus process equivalent dynamics and synchronize their activity. Each …

Examining Artifacts Of The Watershed Segmentation, Emily Jo Armitage

Electronic Theses and Dissertations

The watershed segmentation is an algorithm used to systematically track cell intercalary behaviors during germ band extension of the Drosophila embryo. Neighboring cells share a contracting vertical interface, called a T1, which continues contracting to a single point, a T2, and extending in the horizontal direction to create what is called a T3 interface (Fig. 1). Additionally, higher order vertices called rosettes occur when five or more cells meet at a common vertex. Simulated T2 events demonstrate that cell angle and not noise level in the image contributes to the incorrect detection of artifactual T1s in more acute angled cells …

Quantification Of Dynamic Epithelial Sheet Architecture In Botryllus Schlosseri Using 2-D & 3-D Image Analysis, Roopa Madhu

Electronic Theses and Dissertations

Epithelial tubules form critical structures in various body tissues; how- ever, since they are difficult to access experimentally, their architecture and dynamics are not well understood. Here we examine the dynamic remodeling of epithelial tubes in vivo using a novel and uniquely accessible model system: the extracorporeal vasculature of Botryllus schlosseri (sea squirt). In Botryllus, massive retraction of blood vessels can be triggered without loss of barrier function, through (i) disrupting collagen crosslinking in the basement membrane using β-aminopropionitrile (BAPN); or (ii) disrupting the integrin pathway through inhibition of focal adhesion kinase (FAK). We performed stereographic projections of 3-dimensional …

Consciousness As A Factor In Evolution, Kenneth A. Augustyn

Michigan Tech Publications

What I call the mind began as a non-conscious robotic biochemical process control system in the very earliest forms of life. As life evolved, problems in control became more difficult and exceeded the computational capabilities of the organisms. Nature discovered a means of transcending computable physical processes resulting in non-computational subjective mental capabilities that, while still not conscious, had a degree of genuine autonomy from the physical world. These autonomous subjective wants and goals now affected the course of (but not the mechanism of) evolution. The integrated amalgam of robotic and transrobotic unconscious capabilities eventually gave rise to consciousness, which …

Special Issue On The Third Workshop On Biological Mentality, Kenneth A. Augustyn

Michigan Tech Publications

The Third Workshop on Biological Mentality was held from September 23, 2019 to March 2, 2020 as a series of twenty-one Monday online conferencing sessions, each consisting of a talk followed by a Q&A discussion. Like the two previous workshops [1, 2], the objective of this workshop was to seek a deeper level of understanding the physical foundations of biological mentality (whether conscious or nonconscious).

Complex Ciliary Flows Around Stentor Polymorphus In Solutions Of 2% Buttermilk And Chlamydomonas Reinhardtii, Eliana B. Smithstein

Scripps Senior Theses

Stentor are large, unicellular ciliates of the Heterotricha order. They live in both freshwater and marine habitats and are mostly found in ponds. I studied Stentor polymorphus, which is a species of Stentor only recently discovered to be lab culturable. They range from 0.5-1.5mm in length and are unusual because they live with endosymbiotic algae and are much more likely than other, more widely studied, species of Stentor to form aggregates while they are eating. There are three main components to this thesis: First, I established protocols for keeping a viable S. polymorphus culture, since no protocols had been …