Biophysics Commons^™

A Balanced Approach To Adaptive Probability Density Estimation, Julio Kovacs, Cailee Helmick, Willy Wriggers

Mechanical & Aerospace Engineering Faculty Publications

Our development of a Fast (Mutual) Information Matching (FIM) of molecular dynamics time series data led us to the general problem of how to accurately estimate the probability density function of a random variable, especially in cases of very uneven samples. Here, we propose a novel Balanced Adaptive Density Estimation (BADE) method that effectively optimizes the amount of smoothing at each point. To do this, BADE relies on an efficient nearest-neighbor search which results in good scaling for large data sizes. Our tests on simulated data show that BADE exhibits equal or better accuracy than existing methods, and visual tests …

Computing Spatiotemporal Heat Maps Of Lipid Electropore Formation: A Statistical Approach, Willy Wriggers, Frederica Castellani, Julio A. Kovacs, P. Thomas Vernier

Mechanical & Aerospace Engineering Faculty Publications

We extend the multiscale spatiotemporal heat map strategies originally developed for interpreting molecular dynamics simulations of well-structured proteins to liquids such as lipid bilayers and solvents. Our analysis informs the experimental and theoretical investigation of electroporation, that is, the externally imposed breaching of the cell membrane under the influence of an electric field of sufficient magnitude. To understand the nanoscale architecture of electroporation, we transform time domain data of the coarse-grained interaction networks of lipids and solvents into spatial heat maps of the most relevant constituent molecules. The application takes advantage of our earlier graph-based activity functions by accounting for …

Characterization And Analysis Of Real-Time Capillary Convective Pcr Toward Commercialization, Xianbo Qiu, Shiyin Zhang, Lanju Mei, Di Wu, Ke Li, Shengxiang Ge, Xiangzhong Ye, Ningshao Xia, Michael G. Mauk

Mechanical & Aerospace Engineering Faculty Publications

Almost all the reported capillary convective polymerase chain reaction (CCPCR) systems to date are still limited to research use stemming from unresolved issues related to repeatability, reliability, convenience, and sensitivity. To move CCPCR technology forward toward commercialization, a couple of critical strategies and innovations are discussed here. First, single- and dual-end heating strategies are analyzed and compared between each other. Especially, different solutions for dual-end heating are proposed and discussed, and the heat transfer and fluid flow inside the capillary tube with an optimized dual-end heating strategy are analyzed and modeled. Second, real-time CCPCR is implemented with light-emitting diode and …

Quantitative Limits On Small Molecule Transport Via The Electropermeome - Measuring And Modeling Single Nanosecond Perturbations, Esin B. Sözer, Zachary A. Levine, P. Thomas Vernier

Bioelectrics Publications

The detailed molecular mechanisms underlying the permeabilization of cell membranes by pulsed electric fields (electroporation) remain obscure despite decades of investigative effort. To advance beyond descriptive schematics to the development of robust, predictive models, empirical parameters in existing models must be replaced with physics- and biology-based terms anchored in experimental observations. We report here absolute values for the uptake of YO-PRO-1, a small-molecule fluorescent indicator of membrane integrity, into cells after a single electric pulse lasting only 6 ns. We correlate these measured values, based on fluorescence microphotometry of hundreds of individual cells, with a diffusion-based geometric analysis of pore-mediated …

Biophysical Tools To Study Cellular Mechanotransduction, Ismeel Muhamed, Farhan Chowdhury, Venkat Maruthamuthu

Mechanical & Aerospace Engineering Faculty Publications

The cell membrane is the interface that volumetrically isolates cellular components from the cell's environment. Proteins embedded within and on the membrane have varied biological functions: reception of external biochemical signals, as membrane channels, amplification and regulation of chemical signals through secondary messenger molecules, controlled exocytosis, endocytosis, phagocytosis, organized recruitment and sequestration of cytosolic complex proteins, cell division processes, organization of the cytoskeleton and more. The membrane's bioelectrical role is enabled by the physiologically controlled release and accumulation of electrochemical potential modulating molecules across the membrane through specialized ion channels (e.g., Na^⁺, Ca²⁺, K^⁺ channels). …

Chloride And Proton Binding In The E. Coli 2cl¯:1h+ Clc Exchanger, Catherine Chenal

Dissertations, Theses, and Capstone Projects

The CLC family of membrane proteins is a ubiquitously expressed class of proton and usually voltage-activated chloride transporters involved in a myriad of physiological functions. Crystallographic structures identify up to three chloride binding sites: external, central and intracellular located in the inner half of the trans-membrane domain. The CLC proteins, except for the kidney isoforms, are gated by the extracellular side-facing gating Glutamate (Ex, E148 in CLC-ec1, the E. coli exchanger), which is thought to undergo a conformational change upon protonation.

To sort out how the thermodynamic paths to H+ coupled Cl¯ binding and conformational change in CLC-ec1 at the …

Beneficial Aerodynamic Effect Of Wing Scales On The Climbing Flight Of Butterflies, Nathan Slegers, Michael Heilman, Jacob Cranford, Amy Lang, John Yoder, Maria Laura Habegger

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

It is hypothesized that butterfly wing scale geometry and surface patterning may function to improve aerodynamic efficiency. In order to investigate this hypothesis, a method to measure butterfly flapping kinematics optically over long uninhibited flapping sequences was developed. Statistical results for the climbing flight flapping kinematics of 11 butterflies, based on a total of 236 individual flights, both with and without their wing scales, are presented. Results show, that for each of the 11 butterflies, the mean climbing efficiency decreased after scales were removed. Data was reduced to a single set of differences of climbing efficiency using are paired t …

Assessment Of Disease Lesion Removal As A Method To Control Chronic Montipora White Syndrome, Silvia Beurmann, Christina M. Runyon, Patrick Videau, Sean M. Callahan, Greta S. Aeby

Research & Publications

Coral colonies in Ka–ne‘ohe Bay, Hawai‘i (USA), are afflicted with the tissue loss disease chronic Montipora white syndrome (cMWS). Here we show that removal of chronic disease lesions is a potential method to slow the progression of cMWS in M. capitata. Over the 24 wk observation period, treatment colonies lost almost half the amount of tissue that was lost by control colonies. The percentage of tissue loss at each sampling interval (mean ± SEM; treatment: 1.17 ± 0.47%, control: 2.25 ± 0.63%) and the rate of tissue loss per day (treatment: 0.13 ± 0.04%, control: 0.27 ± 0.08%) were both …

Identifying The Relevance Of C-Reactive Protein Conformers And The Advancement Of A Membrane Curvature Binding Assay, Carrie Leine Moon

Electronic Theses and Dissertations

Lipid membranes play a vital role in cell signaling processes. Membrane shape and lipid content affect interactions between cellular membranes and proteins. This research focuses on characterizing those interactions and their impact by using various biochemical and biophysical assays. These assays were applied to C-reactive protein (CRP), an immune system protein that interacts with lipid membranes and has at least two forms with different properties. Native, pentameric CRP (pCRP) is found in blood serum and is commonly used as a marker for inflammation. The modified form of CRP (mCRP) binds to the protein C1q, which activates the complement immune response. …

Neuronal Gq Structures In Neurodegeneration, Damian S. Mcaninch

Electronic Theses and Dissertations

This study investigates protein nucleic acid interactions between various proteins and G quadruplex (GQ) forming messenger RNAs (mRNAs) in human neurological disorders. 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) repeat domain containing RNA-binding domain.

Three RGG domain containing RNA-binding proteins, all of which have been implicated in neurological disorders, and their interactions with GQ forming mRNAs, were investigated in this study: fused in sarcoma (FUS), fragile X mental retardation protein …

Code For "Noise-Enhanced Coding In Phasic Neuron Spike Trains", Cheng Ly, Brent D. Doiron

Statistical Sciences and Operations Research Data

This zip file contains Matlab scripts and ode (XPP) files to calculate the statistics of the models in "Noise-Enhanced Coding in Phasic Neuron Spike Trains". This article is published in PLoS ONE.

Exploring The Physics Of Proteins At Molecular Level By Neutron And X-Ray Scattering, Utsab Raj Shrestha

Wayne State University Dissertations

The protein structures revealed by the crystallographic studies have provided the valuable information over the years regarding their biological functions. However, such snapshots of protein fluctuations averaged over time may not be enough to fully capture the underlying biological phenomena. A deeper understanding of the protein dynamics is crucial for elucidating the structural pathways or the transition mechanism from the initial state to the final state necessary for regulating the physical and chemical processes. Hence, the biological activities and functions are mainly governed by the protein conformational dynamics. However, the direct correlation of a wide range of protein dynamics to …

Identification Of Expression And Function Of The Glucagon-Like Peptide-1 Receptor In Gastrointestinal Smooth Muscle, Alexander T. May

Theses and Dissertations

In response to ingestion of nutrients, enteroendocrine L cells secrete the incretin hormone, glucagon-like peptide-1 (GLP-1), to enhance glucose-dependent insulin release. Therapies related to GLP-1 are approved for type 2 diabetes. The GLP-1 receptor (GLP-1R) is expressed in cells of the gastrointestinal tract and elsewhere. In pancreatic beta cells, GLP-1R are coupled to the Gs/cAMP/PKA pathway. The expression and function of GLP-1R in gastrointestinal smooth muscle are not known. Aim. To test the hypothesis that GLP-1 regulates smooth muscle function by acting on GLP-1R expressed on smooth muscle. Methods. Smooth muscle cells (SMC) were isolated and cultured. Expression of GLP-1R …

N-Alkyl 4-Methylamphetamine Enantiomers And The Implication For Potential Modulation Of Abuse Liability And Enhancement Of Psychoactive Drug Targeting., Ramsey Sitta

Theses and Dissertations

Drugs of abuse have a long history in humanity. Currently however, a subject of great interest is the phenylalkylamine family of drugs. Not only is the abuse liability of interest but also the potential therapeutic expansion of the capabilities of this family of drugs by utilizing the unique stereospecific effects of the newly discovered hybrid compounds. Based upon prior data of N-Alkyl 4-MA the enantiomers of N-Methyl, N-Ethyl, and N-Propyl were analyzed in hDAT, hNET, and hSERT. It was found that there was a negative correlation between chain length and potency and dopaminergic component. In agreement with the currently established …

Multifunctional Nanomaterials Utilizing Hybridization Chain Reaction For Molecular Diagnostics And Bioanalytical Applications, Md Muhit Rana

Legacy Theses & Dissertations (2009 - 2024)

DNA nanotechnology has shown great promise in molecular diagnostic, bioanalytical and biomedical applications. The great challenge of detecting target analytes, biomarkers and small molecules, in molecular diagnostics is low yield sensitivity. To address this challenge, different nanomaterials have been used for a long time and to date there is no such cost-effective bioanalytical technique which can detect these target biomarkers (DNA, RNA, circulating DNA/miRNA) or environmental heavy metal ions (Hg2+ and Ag+) in a cost-effective and efficient manner.

Modeling The Binding Of Neurotransmitter Transporter Inhibitors With Molecular Dynamics And Free Energy Calculations, Bernandie Jean

Electronic Theses and Dissertations

The monoamine transporter (MAT) proteins responsible for the reuptake of the neurotransmitter substrates, dopamine, serotonin, and norepinephrine, are drug targets for the treatment of psychiatric disorders including depression, anxiety, and attention deficit hyperactivity disorder. Small molecules that inhibit these proteins can serve as useful therapeutic agents. However, some dopamine transporter (DAT) inhibitors, such as cocaine and methamphetamine, are highly addictive and abusable. Efforts have been made to develop small molecules that will inhibit the transporters and elucidate specific binding site interactions. This work provides knowledge of molecular interactions associated with MAT inhibitors by offering an atomistic perspective that can guide …

Micro-Spectroscopy Of Bio-Assemblies At The Single Cell Level, Jeslin Kera

Honors Undergraduate Theses

In this thesis, we investigate biological molecules on a micron scale in the ultraviolet spectral region through the non-destructive confocal absorption microscopy. The setup involves a combination of confocal microscope with a UV light excitation beam to measure the optical absorption spectra with spatial resolution of 1.4 μm in the lateral and 3.6 μm in the axial direction. Confocal absorption microscopy has the benefits of requiring no labels and only low light intensity for excitation while providing a strong signal from the contrast generated by the attenuation of propagating light due to absorption. This enables spatially resolved measurements of single …

Manipulating Lipid Spreading Domain Formation With Compositional Gradients And Plasmonic Nanoparticles, Chen-Min Hung

CMC Senior Theses

After colliding two solid-supported spreading bilayers of different compositions, we produce a dynamic gradient as the newly-healed bilayer equilibrates. We apply this approach to study the formation of galactosyl ceramide (GalCer) domains. With a single experiment, we are able to explore the effects of varying cholesterol concentration on GalCer domains. To further control domain formation, we aimed to locally heat membranes with embedded plasmonic nanoparticles. However, we discovered a percolation threshold of spreading lipids over the array of nanoparticles. We found that surfaces with gold nanoparticles deposited at an average inter-particle distance of 40 nm inhibited lipid bilayer spreading, but …

Evolution Of The Kinetics And Dynamics Of Heme-Crevice Loop Regulating Chemistry In Human Cytochrome C, Shiloh M. Nold

Graduate Student Theses, Dissertations, & Professional Papers

Cytochrome c, cytc, is a metalloprotein that plays primary roles in electron transport and intrinsic apoptotic pathways. Much of the chemistry that cytc is involved with is regulated by a highly conserved region known as the heme crevice loop, consisting of residues 70-85. Only three of these residues (those at positions 81, 83 and 85) are not universally conserved within the evolutionary timeline. Here I look to elucidate possible evolutionary roles for several of the key residues known to be important in regulating heme chemistry of cytc.

I first address the role that lysine …

Structural Basis Of Membrane Protein Scaffolding And Signaling In Human Disease, Joshua Holcomb

Wayne State University Dissertations

Protein structural elucidation by means of X-ray crystallography is a powerful approach for both insight into a proteins biophysical properties and function. To date X-ray crystallography remains the gold standard in high resolution structural determination and serves as the basis for rational drug design for the purpose of combating a number of human diseases. Such an approach also allows for the exploitation of how various proteins interact with their substrates providing a molecular basis for their physiological function. In this dissertation, using X-ray crystallographic analysis along with other biophysical characterization methods, we seek to understand the mechanistic foundation for which …