Coarse Graining to Invesitigate Peptide-Lipid Interactions

Experimental characterization of molecular details is challenging, and although single molecule experiments have gained prominence, oligomer characterization remains largely unexplored. The ability to monitor the time evolution of individual molecules while they self assemble is essential in providing mechanistic insights about biological events. Molecular dynamics (MD) simulations can fill the gap in knowledge between single molecule experiments and ensemble studies like NMR, and are increasingly used to gain a better understanding of microscopic properties. Coarse-grained (CG) models aid in both exploring longer length and time scale molecular phenomena, and narrowing down the key interactions responsible for significant system characteristics. Over the past decade, CG techniques have made a significant impact in understanding physicochemical processes. However, the realm of peptide-lipid interfacial interactions, primarily binding, partitioning and folding of amphipathic peptides, remains largely unexplored compared to peptide folding in solution. The main drawback of existing CG models is the inability to capture environmentally sensitive changes in dipolar interactions, which are indigenous to protein folding, and lipid dynamics. We have used the Drude oscillator approach to incorporate structural polarization and dipolar interactions in CG beads to develop a minimalistic peptide model, WEPPROM (Water Explicit Polarizable PROtein Model), and a lipid model WEPMEM (Water Explicit Polarizable MEmbrane Model). The addition of backbone dipolar interactions in a CG model for peptides enabled us to achieve alpha-beta secondary structure content de novo, without any added bias. As a prelude to studying amphipathic peptide-lipid membrane interactions, the balance between hydrophobicity and backbone dipolar interactions in driving ordered peptide aggregation in water and at a hydrophobic-hydrophilic interface, was explored. We found that backbone dipole interactions play a crucial role in driving ordered peptide aggregation, both in water and at hydrophobic-hydrophilic interfaces; while hydrophobicity is more relevant for aggregation in water. A zwitterionic (POPC: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and an anionic lipid (POPS: 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine) are used as model lipids for WEPMEM. The addition of head group dipolar interactions in lipids significantly improved structural, dynamic and dielectric properties of the model bilayer. Using WEPMEM and WEPPROM, we studied membrane-induced peptide folding of a cationic antimicrobial peptide with anticancer activity, SVS-1. We found that membrane-induced peptide folding is driven by both (a) cooperativity in peptide self interaction and (b) cooperativity in membrane-peptide interactions. The dipolar interactions between the peptide and the lipid head-groups contribute to stabilizing folded conformations. The role of monovalent ion size and peptide concentration in driving lipid domain formation in anionic/zwitterionic lipid mixtures was also investigated. Our study suggest monovalent ion size to be a crucial determinant of interaction with lipid head groups, and hence domain formation in lipid mixtures. This study reinforces the role of dipole interactions in protein folding, lipid membrane properties, membrane induced peptide folding and lipid domain formation. Therefore, the models developed in this thesis can be used to explore a multitude of biomolecular processes, both at longer time-scales and larger system sizes.

Observed Teleconnections in Northern Winter: Subseasonal Evolution and Tropical Linkages

Teleconnections refer to the climate variability links between non-contiguous geographic regions, and tend to be associated with variability in both space and time of the climate’s semi-permanent circulation features. Teleconnections are well-developed in Northern winter, when they influence subseasonal-to-seasonal climate variability, notably, in surface temperature and precipitation. This work is comprised of four independent studies that improve understanding of tropical-extratropical teleconnections and their surface climate responses, subseasonal teleconnection evolution, and the utility of teleconnections in attribution of extreme climate events. After an introduction to teleconnection analysis as well as the major teleconnection patterns and associated climatic footprints manifest during Northern winter, the lagged impact of the Madden-Julian Oscillation (MJO) on subseasonal climate variability is presented. It is found that monitoring of MJO-related velocity potential anomalies is sufficient to predict MJO impacts. These impacts include, for example, the development of significant positive temperature anomalies over the eastern United States one to three weeks following an anomalous convective dipole with enhanced (suppressed) convection centered over the Indian Ocean (western Pacific). Subseasonal teleconnection evolution is assessed with respect to the Pacific-North America (PNA) pattern and the North Atlantic Oscillation (NAO). This evolution is analyzed both in the presence and absence of MJO-related circulation anomalies. It is found that removal of the MJO results only in small shifts in the centers of action of the NAO and PNA, and that in either case there is a small but significant lag in which the NAO leads a PNA pattern of opposite phase. Barotropic vorticity analysis suggests that this relationship may result in part from excitation of Rossby waves by the NAO in the Asian waveguide. An attempt is made to elegantly differentiate between the MJO extratropical response and patterns of variability more internal to the extratropics. Analysis of upper-level streamfunction anomalies is successful in this regard, and it is suggested that this is the preferred method for the real time monitoring of tropical-extratropical teleconnections. The extreme 2013-2014 North American winter is reconstructed using teleconnection analysis, and it is found that the North Pacific Oscillation-West Pacific (NPO/WP) pattern was the leading contributor to climate anomalies over much of North America. Such attribution is cautionary given the propensity to implicate the tropics for all midlatitude climate anomalies based on the El Niño-Southern Oscillation (ENSO) paradigm. A recent hypothesis of such tropical influence is presented and challenged.

Geochemistry of crustal formation and evolution

Terrestrial planets produce crusts as they differentiate. The Earth’s bi-modal crust, with a high-standing granitic continental crust and a low-standing basaltic oceanic crust, is unique in our solar system and links the evolution of the interior and exterior of this planet. Here I present geochemical observations to constrain processes accompanying crustal formation and evolution. My approach includes geochemical analyses, quantitative modeling, and experimental studies. The Archean crustal evolution project represents my perspective on when Earth’s continental crust began forming. In this project, I utilized critical element ratios in sedimentary records to track the evolution of the MgO content in the upper continental crust as a function time. The early Archean subaerial crust had >11 wt. % MgO, whereas by the end of Archean its composition had evolved to about 4 wt. % MgO, suggesting a transition of the upper crust from a basalt-like to a more granite-like bulk composition. Driving this fundamental change of the upper crustal composition is the widespread operation of subduction processes, suggesting the onset of global plate tectonics at ~ 3 Ga (Abstract figure). Three of the chapters in this dissertation leverage the use of Eu anomalies to track the recycling of crustal materials back into the mantle, where Eu anomaly is a sensitive measure of the element’s behavior relative to neighboring lanthanoids (Sm and Gd) during crustal differentiation. My compilation of Sm-Eu-Gd data for the continental crust shows that the average crust has a net negative Eu anomaly. This result requires recycling of Eu-enriched lower continental crust to the mantle. Mass balance calculations require that about three times the mass of the modern continental crust was returned into the mantle over Earth history, possibly via density-driven recycling. High precision measurements of Eu/Eu* in selected primitive glasses of mid-ocean ridge basalt (MORB) from global MORs, combined with numerical modeling, suggests that the recycled lower crustal materials are not found within the MORB source and may have at least partially sank into the lower mantle where they can be sampled by hot spot volcanoes. The Lesser Antilles Li isotope project provides insights into the Li systematics of this young island arc, a representative section of proto-continental crust. Martinique Island lavas, to my knowledge, represent the only clear case in which crustal Li is recycled back into their mantle source, as documented by the isotopically light Li isotopes in Lesser Antilles sediments that feed into the fore arc subduction trench. By corollary, the mantle-like Li signal in global arc lavas is likely the result of broadly similar Li isotopic compositions between the upper mantle and bulk subducting sediments in most arcs. My PhD project on Li diffusion mechanism in zircon is being carried out in extensive collaboration with multiple institutes and employs analytical, experimental and modeling studies. This ongoing project, finds that REE and Y play an important role in controlling Li diffusion in natural zircons, with Li partially coupling to REE and Y to maintain charge balance. Access to state-of-art instrumentation presented critical opportunities to identify the mechanisms that cause elemental fractionation during laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analysis. My work here elucidates the elemental fractionation associated with plasma plume condensation during laser ablation and particle-ion conversion in the ICP.

Quantitative Derivation of Effective Evolution Equations for the Dynamics of Bose-Einstein Condensates

This thesis proves certain results concerning an important question in non-equilibrium quantum statistical mechanics which is the derivation of effective evolution equations approximating the dynamics of a system of large number of bosons initially at equilibrium (ground state at very low temperatures). The dynamics of such systems are governed by the time-dependent linear many-body Schroedinger equation from which it is typically difficult to extract useful information due to the number of particles being large. We will study quantitatively (i.e. with explicit bounds on the error) how a suitable one particle non-linear Schroedinger equation arises in the mean field limit as number of particles N → ∞ and how the appropriate corrections to the mean field will provide better approximations of the exact dynamics. In the first part of this thesis we consider the evolution of N bosons, where N is large, with two-body interactions of the form N³ᵝv(Nᵝ⋅), 0≤β≤1. The parameter β measures the strength and the range of interactions. We compare the exact evolution with an approximation which considers the evolution of a mean field coupled with an appropriate description of pair excitations, see [18,19] by Grillakis-Machedon-Margetis. We extend the results for 0 ≤ β < 1/3 in [19, 20] to the case of β < 1/2 and obtain an error bound of the form p(t)/Nᵅ, where α>0 and p(t) is a polynomial, which implies a specific rate of convergence as N → ∞. In the second part, utilizing estimates of the type discussed in the first part, we compare the exact evolution with the mean field approximation in the sense of marginals. We prove that the exact evolution is close to the approximate in trace norm for times of the order o(1)√N compared to log(o(1)N) as obtained in Chen-Lee-Schlein [6] for the Hartree evolution. Estimates of similar type are obtained for stronger interactions as well.

SOVLENT REACTIVITY AND INTERFACE EVOLUTION AT MODEL ELECTRODES FOR ENERGY APPLICATIONS

The Li-ion rechargeable battery (LIB) is widely used as an energy storage device, but has significant limitations in battery cycle life and safety. During initial charging, decomposition of the ethylene carbonate (EC)-based electrolytes of the LIB leads to the formation of a passivating layer on the anode known as the solid electrolyte interphase (SEI). The formation of an SEI has great impact on the cycle life and safety of LIB, yet mechanistic aspects of SEI formation are not fully understood. In this dissertation, two surface science model systems have been created under ultra-high vacuum (UHV) to probe the very initial stage of SEI formation at the model carbon anode surfaces of LIB. The first model system, Model System I, is an lithium-carbonate electrolyte/graphite C(0001) system. I have developed a temperature programmed desorption/temperature programmed reaction spectroscopy (TPD/TPRS) instrument as part of my dissertation to study Model System I in quantitative detail. The binding strengths and film growth mechanisms of key electrolyte molecules on model carbon anode surfaces with varying extents of lithiation were measured by TPD. TPRS was further used to track the gases evolved from different reduction products in the early-stage SEI formation. The branching ratio of multiple reaction pathways was quantified for the first time and determined to be 70.% organolithium products vs. 30% inorganic lithium product. The obtained branching ratio provides important information on the distribution of lithium salts that form at the very onset of SEI formation. One of the key reduction products formed from EC in early-stage SEI formation is lithium ethylene dicarbonate (LEDC). Despite intensive studies, the LEDC structure in either the bulk or thin-film (SEI) form is unknown. To enable structural study, pure LEDC was synthesized and subject to synchrotron X-ray diffraction measurements (bulk material) and STM measurements (deposited films). To enable studies of LEDC thin films, Model System II, a lithium ethylene dicarbonate (LEDC)-dimethylformamide (DMF)/Ag(111) system was created by a solution microaerosol deposition technique. Produced films were then imaged by ultra-high vacuum scanning tunneling microscopy (UHV-STM). As a control, the dimethylformamide (DMF)-Ag(111) system was first prepared and its complex 2D phase behavior was mapped out as a function of coverage. The evolution of three distinct monolayer phases of DMF was observed with increasing surface pressure — a 2D gas phase, an ordered DMF phase, and an ordered Ag(DMF)2 complex phase. The addition of LEDC to this mixture, seeded the nucleation of the ordered DMF islands at lower surface pressures (DMF coverages), and was interpreted through nucleation theory. A structural model of the nucleation seed was proposed, and the implication of ionic SEI products, such as LEDC, in early-stage SEI formation was discussed.

ANALYSIS OF MACROINVERTEBRATE COMMUNITIES IN SEASONAL WETLANDS THROUGH TIME, ACROSS SPACE, AND USING SPECIES TRAITS

Restoration of natural wetlands may be informed by macroinvertebrate community composition. Macroinvertebrate communities of wetlands are influenced by environmental characteristics such as vegetation, soil, hydrology, land use, and isolation. This dissertation explores multiple approaches to the assessment of wetland macroinvertebrate community composition, and demonstrates how these approaches can provide complementary insights into the community ecology of aquatic macroinvertebrates. Specifically, this work focuses on macroinvertebrates of Delmarva Bays, isolated seasonal wetlands found on Maryland’s eastern shore. A comparison of macroinvertebrate community change over a nine years in a restored wetland complex indicated that the macroinvertebrate community of a rehabilitated wetlands more rapidly approximated the community of a reference site than did a newly created wetland. The recovery of a natural macroinvertebrate community in the rehabilitated wetland indicated that wetland rehabilitation should be prioritized over wetland creation and long-term monitoring may be needed to evaluate restoration success. This study also indicated that characteristics of wetland vegetation reflected community composition. The connection between wetland vegetation and macroinvertebrate community composition led to a regional assessment of predaceous diving beetle (Coleoptera: Dytiscidae) community composition in 20 seasonal wetlands, half with and half without sphagnum moss (Sphagnum spp.). Species-level identifications indicated that wetlands with sphagnum support unique and diverse assemblages of beetles. These patterns suggest that sphagnum wetlands provide habitat that supports biodiversity on the Delmarva Peninsula. To compare traits of co-occurring beetles, mandible morphology and temporal and spatial variation were measured between three species of predaceous diving beetles. Based on mandible architecture, all species may consume similarly sized prey, but prey characteristics likely differ in terms of piercing force required for successful capture and consumption. Therefore, different assemblages of aquatic beetles may have different effects on macroinvertebrate community structure. Integrating community-level and species-level data strengthens the association between individual organisms and their ecological role. Effective restoration of imperiled wetlands benefits from this integration, as it informs the management practices that both preserve biodiversity and promote ecosystem services.