Session B04: Biophysics and Soft Condensed Matter I

Models of single molecule dynamics from single photon detections: a Bayesian nonparametric approach

Fluorescence time traces report on dynamical properties of biomolecules. The basic unit of information contained therein is the individual photon. Single photons carry instantaneous information from the biomolecule, from which they are emitted, to the detector on rapid, sub-microsecond, timescales. Thus, from confocal microscopy it is theoretically possible to monitor biomolecular dynamics from hundreds to thousands of photons arrivals at those timescales. In practice, however, signals are stochastic and to deduce information through traditional means, such as fluorescence correlation spectroscopy (FCS) and related techniques, fluorescence signals are collected and temporally auto-correlated over several minutes. Here, we exploit novel mathematical tools, namely Bayesian nonparametrics, that allow us to deduce in a principled fashion the same information normally deduced from FCS but from the direct analysis of significantly smaller datasets starting from individual photon arrivals. We discuss the implications of this method in helping dramatically reduce phototoxic damage on the sample and the ability to monitor out-of-equilibrium processes.   

Using THz Spectroscopy to Identify Fibrotic Tissue due to Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is a chronic lung disease that causes irreversible progressive scarring of interstitial lung tissue, and is almost always terminal within 3-5 years. Though there are known risk factors, the exact cause of the disease remains unknown. Current IPF diagnosis is challenging because it is based on visual tests (such as optical tissue images and high-resolution micro CT scans) that can be influenced by interobserver variation. Currently there is no objective, quantifiable method of diagnosing IPF. Due to the success in using THz spectroscopy to identify and image specific biomarkers in other systems, we are developing THz bioimaging histological methods that can provide an objective way to identify fibrotic tissue and diagnose idiopathic pulmonary fibrosis. I will discuss preliminary results showing we can distinguish different components in tissue samples. Current imaging times are long (several hours), and so I will also discuss our progress in constructing a high-speed THz imaging system.   

Dynamics of Solids Irradiated by UED beams

The remarkable success of the X-ray free-electron lasers (XFELs), and their ability to image biological macromolecules while minimizing secondary radiation damage due photoelectrons when using femtosecond pulses raises the question of whether this can also be achieved using pulsed Ultrafast Electron Diffraction (UED) beams. The limiting factor for both Cryo-EM and x-ray sources, e.g. XFEL, for imaging or capturing a diffraction pattern is radiation damage. Radiation damage is caused by undesirable inelastic excitations by the beam on the sample. In this paper we use excited state molecular dynamics simulations to investigate time resolved radiation damage mechanisms in soft matter, as a function of pulse parameters (such as emittance, duration, and brightness).   

Monatomic Ion Coordination in Proteins

In order to understand the role of ions in proteins, it is important to have an accurate description of the interactions between bound ions and atoms common in proteins. An automated analysis method was developed to analyze monatomic ions contained in crystal structures in the RCSB Protein Data Bank (PDB). The coordination characteristics of the most prevalent monovalent cations in the PDB were analyzed through the radial distribution functions of oxygen atoms around ions. It is known that sodium ions coordinate oxygen atoms within about a 6 \AA \ radius, with a clear first “coordination shell,” similar to a hydration shell in bulk water, and a secondary shell also typically visible. However, oxygen atoms are not the only atoms that can coordinate cations, and coordinating atoms for anions are far less understood than those for cations. The analysis was extended to explore the distributions of other coordinating atoms, namely nitrogen, sulfur, and carbon, as well as anions and multivalent cations. It was observed that many ions are preferentially coordinated by certain atoms, for example, zinc specifically is largely coordinated by sulfur. Additionally, quantitative values were calculated to describe the locations and strengths of the coordination shells for each ion.   

A Comparative Study of X-ray Photoelectron Spectroscopy, X-ray Fluorescence, and Ion Beam Analysis on Homogeneous Thin Solid Films of \textmu L-sized Blood Droplets solidified via Hyper-Hydrophilic Coatings (HemaDrop$^{\mathrm{TM}})$

Blood diagnostics require \textasciitilde 7 mL of blood per test and takes days. Frequent drawing of blood induces hospital-acquired anemia in premature infants and ill patients. Decreasing volume needed and improving analysis speed and accuracy can enhance healthcare. HemaDrop$^{\mathrm{TM}}$, a hyper-hydrophilic coating, can solidify \textmu L-sized blood droplets in minutes into Homogeneous Thin Solid Films (HTSFs) without phase separation. Blood HTSFs were tested for accuracy of electrolytes (Na, K, Mg, Ca, Cl) and heavy metals (Fe) measurements from $\mu $L drops. Quantitative blood electrolyte compositions via SIMNRA simulations on successive IBA spectra on HTSFs are compared to measurements via XPS and XRF. Relative error analysis between different HTSFs and damage curve analysis of repeated measurements on the same HTSF establish reproducibility to \textless 10{\%}. Comparison of compositional measurements of blood and balanced saline solution (BSS) with known concentration of BSS aims to allow direct conversion of atomic {\%} to concentration in mg/dL, the main metric in blood diagnostics.