Physics Commons^™

Splitting Nodes And Linking Channels: A Method For Assembling Biocircuits From Stochastic Elementary Units, Cameron Ferwerda, Ovidiu Lipan

Physics Faculty Publications

Akin to electric circuits, we construct biocircuits that are manipulated by cutting and assembling channels through which stochastic information flows. This diagrammatic manipulation allows us to create a method which constructs networks by joining building blocks selected so that (a) they cover only basic processes; (b) it is scalable to large networks; (c) the mean and variance-covariance from the Pauli master equation form a closed system; and (d) given the initial probability distribution, no special boundary conditions are necessary to solve the master equation. The method aims to help with both designing new synthetic signaling pathways and quantifying naturally existing …

Exposure Of Fibrinogen And Thrombin To Nitric Oxide Donor Prolinonoate Affects Fibrin Clot Properties, Christine C. Helms, Shannon Kapadia, Anne C. Gilmore, Zhexi Lu, Swati Basu, Daniel B. Kim-Shapiro

Physics Faculty Publications

Fibrin fibers form the structural backbone of blood clots. The structural properties of fibrin clots are highly dependent on formation kinetics. Environmental factors such as protein concentration, pH, salt, and protein modification, to name a few, can affect fiber kinetics through altered fibrinopeptide release, monomer association, and/or lateral aggregation. The objective of our study was to determine the effect of thrombin and fibrinogen exposed to nitric oxide on fibrin clot properties. ProliNONOate (5 [mu]mol/l) was added to fibrinogen and thrombin before clot initiation and immediately following the addition of thrombin to the fibrinogen solution. Resulting fibrin fibers were probed with …

Mechanisms Of Hemolysis-Associated Platelet Activation, Christine C. Helms, M. Marvel, W. Zhao, M. Stahle, R. Vest, G. J. Kato, J. S. Lee, G. Christ, M. T. Gladwin, R. R. Hantgan, D. B. Kim-Shapiro

Physics Faculty Publications

Background

Intravascular hemolysis occurs after blood transfusion, in hemolytic anemias, and in other conditions, and is associated with hypercoagulable states. Hemolysis has been shown to potently activate platelets in vitro and in vivo, and several mechanisms have been suggested to account for this, including: (i) direct activation by hemoglobin (Hb); (ii) increase in reactive oxygen species (ROS); (iii) scavenging of nitric oxide (NO) by released Hb; and (iv) release of intraerythrocytic ADP.

Objective

To elucidate the mechanism of hemolysis-mediated platelet activation.

Methods

We used flow cytometry to detect PAC-1 binding to activated platelets for in vitro experiments, and a …

Hemoglobin-Mediated Nitric Oxide Signaling, Christine C. Helms, D. B. Kim-Shapiro

Physics Faculty Publications

The rate that hemoglobin reacts with nitric oxide (NO) is limited by how fast NO can diffuse into the heme pocket. The reaction is as fast as any ligand/protein reaction can be and the result, when hemoglobin is in its oxygenated form, is formation of nitrate in what is known as the dioxygenation reaction. As nitrate, at the concentrations made through the deoxygenation reaction, is biologically inert, the only role hemoglobin was once thought to play in NO signaling was to inhibit it. However, there are now several mechanisms that have been discovered by which hemoglobin may preserve, control, and …

A Modular Fibrinogen Model That Captures The Stress-Strain Behavior Of Fibrin Fibers, Rodney D. Averett, Bryant Menn, Eric H. Lee, Christine C. Helms, Thomas Barker, Martin Guthold

Physics Faculty Publications

We tested what to our knowledge is a new computational model for fibrin fiber mechanical behavior. The model is composed of three distinct elements: the folded fibrinogen core as seen in the crystal structure, the unstructured α-C connector, and the partially folded α-C domain. Previous studies have highlighted the importance of all three regions and how they may contribute to fibrin fiber stress-strain behavior. Yet no molecular model has been computationally tested that takes into account the individual contributions of all these regions. Constant velocity, steered molecular dynamics studies at 0.025 Å/ps were conducted on the folded fibrinogen …

Α−Α Cross-Links Increase Fibrin Fiber Elasticity And Stiffness, Christine C. Helms, Robert A.S. Ariens, S. Uitte De Willige, Kristina F. Standeven, Martin Guthold

Physics Faculty Publications

Fibrin fibers, which are ∼100 nm in diameter, are the major structural component of a blood clot. The mechanical properties of single fibrin fibers determine the behavior of a blood clot and, thus, have a critical influence on heart attacks, strokes, and embolisms. Cross-linking is thought to fortify blood clots; though, the role of α–α cross-links in fibrin fiber assembly and their effect on the mechanical properties of single fibrin fibers are poorly understood. To address this knowledge gap, we used a combined fluorescence and atomic force microscope technique to determine the stiffness (modulus), extensibility, and elasticity of …

The Mechanical Stress–Strain Properties Of Single Electrospun Collagen Type I Nanofibers, Christine C. Helms, Corentin Coulais, Martin Guthold

Physics Faculty Publications

Knowledge of the mechanical properties of electrospun fibers is important for their successful application in tissue engineering, material composites, filtration and drug delivery. In particular, electrospun collagen has great potential for biomedical applications due to its biocompatibility and promotion of cell growth and adhesion. Using a combined atomic force microscopy (AFM)/optical microscopy technique, the single fiber mechanical properties of dry, electrospun collagen type I were determined. The fibers were electrospun from a 80 mg ml⁻¹ collagen solution in 1,1,1,3,3,3-hexafluro-2-propanol and collected on a striated surface suitable for lateral force manipulation by AFM. The small strain modulus, calculated from three-point …

Strength And Failure Of Fibrin Fiber Branch Points, Christine C. Helms, E. A. Sparks, C. Der Laughian, Martin Guthold

Physics Faculty Publications

Blood clots form rapidly in the event of vascular injury, to prevent blood loss. They may also form in undesired places, causing heart attacks, strokes, and other diseases. Blood clots can rupture, and fragments of the clotmay lodge in distal blood vessels, causing, for example, ischemic strokes or embolisms. Thus, there has been great interest in understanding the mechanical behavior and failure mechanisms of blood clots and their constituents. To develop a mechanically realistic model of a blood clot, knowledge of the mechanical properties of its constituents is required. The major structural component providing mechanical strength to the clot is …

The Mechanical Properties Of Single Fibrin Fibers, W. Liu, Christine C. Helms, E. A. Sparks, Martin Guthold

Physics Faculty Publications

Background:

Blood clots perform the mechanical task of stemming the flow of blood.

Objectives:

To advance understanding and realistic modeling of blood clot behavior we determined the mechanical properties of the major structural component of blood clots, fibrin fibers.

Methods:

We used a combined atomic force microscopy (AFM)/fluorescence microscopy technique to determine key mechanical properties of single crosslinked and uncrosslinked fibrin fibers.

Results and conclusions:

Overall, full crosslinking renders fibers less extensible, stiffer, and less elastic than their uncrosslinked counterparts. All fibers showed stress relaxation behavior (time-dependent weakening) with a fast and a slow relaxation time, 2 and 52 s. …

Measurement Of Γ-Emission Branching Ratios For 154,156,158Gd Compound Nuclei: Tests Of Surrogate Nuclear Reaction Approximations For (N,Γ) Cross Sections, N. D. Scielzo

Physics Faculty Publications

The surrogate nuclear reaction method can be used to determine neutron-induced reaction cross sections from measured decay properties of a compound nucleus created using a different reaction and calculated formation cross sections. The reliability of (n,γ) cross sections determined using the Weisskopf-Ewing and ratio approximations are explored for the ^{155, 157}Gd(n,γ) reactions. Enriched gadolinium targets were bombarded with 22-MeV protons and γ rays were detected in coincidence with scattered protons using the Silicon Telescope Array for Reaction Studies/Livermore-Berkeley Array for Collaborative Experiments (STARS/LiBerACE) silicon and germanium detector arrays. The γ-emission probabilities for the ^{154, 156, …}

The Mechanical Properties Of Individual, Electrospun Fibrinogen Fibers, Christine C. Helms, Corentin Coulais, Manoj Namboothiry, David L. Carroll, Roy R. Hantgan, Martin Guthold

Physics Faculty Publications

We used a combined atomic force microscope (AFM)/fluorescence microscope technique to study the mechanical properties of individual, electrospun fibrinogen fibers in aqueous buffer. Fibers (average diameter 208 nm) were suspended over 12 μm-wide grooves in a striated, transparent substrate. The AFM, situated above the sample, was used to laterally stretch the fibers and to measure the applied force. The fluorescence microscope, situated below the sample, was used to visualize the stretching process. The fibers could be stretched to 2.3 times their original length before breaking; the breaking stress was 22·10⁶ Pa. We collected incremental stress-strain curves to determine the …