Expertise in physics has been traditionally studied in cognitive science, where physics expertise is understood through the difference between novice and expert problem solving skills. The cognitive perspective of physics experts only create a partial model of physics expertise and does not take into account the development of physics experts in the natural context of research. This dissertation takes a social and cultural perspective of learning through apprenticeship to model the development of physics expertise of physics graduate students in a research group. I use a qualitative methodological approach of an ethnographic case study to observe and video record the common practices of graduate students in their biophysics weekly research group meetings. I recorded notes on observations and conduct interviews with all participants of the biophysics research group for a period of eight months. I apply the theoretical framework of Communities of Practice to distinguish the cultural norms of the group that cultivate physics expert practices. Results indicate that physics expertise is specific to a topic or subfield and it is established through effectively publishing research in the larger biophysics research community. The participant biophysics research group follows a learning trajectory for its students to contribute to research and learn to communicate their research in the larger biophysics community. In this learning trajectory students develop expert member competencies to learn to communicate their research and to learn the standards and trends of research in the larger research community. Findings from this dissertation expand the model of physics expertise beyond the cognitive realm and add the social and cultural nature of physics expertise development. This research also addresses ways to increase physics graduate student success towards their PhD. and decrease the 48% attrition rate of physics graduate students. Cultivating effective research experiences that give graduate students agency and autonomy beyond their research groups gives students the motivation to finish graduate school and establish their physics expertise.

All biological cell membranes maintain an electric transmembrane potential of around 100 mV, due in part to an asymmetric distribution of charged phospholipids across the membrane. This asymmetry is crucial to cell health and physiological processes such as intracell signaling, receptor-mediated endocytosis, and membrane protein conformation and function as well as active processes involving flippase and floppase proteins. Despite the biological significance, there are limited studies linking the consequences of lipid asymmetry to critical membrane properties and processes involving ion channels. One reason for this is the scarcity of reliable methods to create artificial membrane systems that incorporate both transverse lipid asymmetry and ion channels. Experimental artificial membrane systems incorporate essential cell membrane structures, namely the phospholipid bilayer, in a controllable manner where specific properties and processes can be isolated and examined in an environment much simpler than living systems. It is of particular interest to study asymmetry in transverse lipid composition across the phospholipid bilayer on such a system to probe the effects of the lipid composition and asymmetric arrangement of these lipids on the physicochemical properties of the membrane. By doing so, an understanding of how membrane asymmetry dictates membrane properties and in turn impacts cellular processes will be achieved. The primary goal of this thesis is to develop a platform for fabricating and characterizing compositionally controlled planar, free-standing, asymmetric membranes. This asymmetry was qualitatively demonstrated using a fluorescence quenching assay, and it has been quantified using a combination of anionic and zwitterionic lipids in concert with a patch-clamp amplifier system. Initial measurements of a transmembrane potential on a partially asymmetric bilayer were found to be between 10 and 25 mV. Increasing membrane charge asymmetry increases the offset voltage, as expected, and also modifies the stiffness of the membrane. These initial successes demonstrate a viable pathway to fabricate and quantitatively characterize asymmetric bilayers that can be extended to accommodate more complex membrane processes in the future.

Protein aggregation is deleterious to human health and detrimental to therapeutic shelf-life. The physical processes that induce aggregation are the same processes that drive productive folding reactions. As such, protein aggregation is a non-productive form of protein folding. To gain insight into the steps that serve as a partition between the folding and aggregation reactions, the folding mechanisms of several β-rich proteins with links to human disease or medicine were examined. In the ALS-linked protein, SOD1, a subpopulation of the unfolded ensemble is found to be a common source of both nonnative structure and frustrated folding. These behaviors are only observed upon the reduction of the intrinsic disulfide bond, indicating that this covalent interaction wards against aggregation. The nonnative structure presents an attractive target for the development of new therapeutic agents. In VH domains from therapeutic mAbs, the intramolecular disulfide bond protects against aggregation. However, it can also introduce complexity to the folding mechanism. This complexity is linked to the formation of a strained orientation of the disulfide bond. This strained orientation of the disulfide in certain VH domains is energetically unfavorable enough to disrupt the formation of the disulfide in the full length mAbs. The novel relationship observed between disulfide orientation, folding complexity, and incomplete oxidation warrants further examination in other Ig domains. Overall, these results demonstrate that mapping the folding free energy landscape for proteins with roles in human disease or therapeutics can provide valuable insights for developing and improving treatment options.

In this study we have investigated the frequency dependence of bilayer lipid membranes for a series of glycerylmonoolein/ n-decane bilayers in various aqueous ionic solutions containing the ionophore valinomycin. Reliable values of membrane capacitance and conductance were obtained over the frequency range 0.2 - 200 KHz using an automatic balancing bridge under the control of a microprocessor unit. The admittance data was then normalized and curve-fitted to produce relaxation times and amplitudes from which the kinetic rate parameters, as deduced from a single slab dielectric membrane model, were calculated. These ac experimental rate constants were then compared with those obtained from charge-pulse relaxation methods.

Alzheimer's Disease (AD) is a devastating neurodegenerative disease that is characterized by brain atrophy, neuronal and synaptic loss, cognitive decline, trouble handling activities of daily life, and ultimately leads to death. Worldwide, at least 30 million people suffer from AD, with 5.8 million suffering in the US alone. Despite extensive basic and clinical research, the underlying molecular mechanisms behind AD remain largely unknown. There are four FDA-approved compounds are used for alleviating symptoms but have no curative potency. The first potentially disease-modifying AD drug, aducanumb, was approved by FDA in June 2021. The main histopathological traits of AD are the Amyloid-beta (Aβ) peptide and the tau protein. Aβ aggregates to form extracellular plaques in brain parenchyma and vasculature while tau forms intraneuronal tangles. Aβ is produced by enzymatic cleavage of the amyloid precursor protein (APP) in the brain. Once APP cleavage occurs, Ab monomers either aggregate extracellularly to form buildups of sticky plaque or embed themselves within the neuronal cell membrane to form pores, causing homeostatic dysregulation and eventually cell death. The mechanism of membrane pores formed by Ab and the pore structure remain to be characterized. This study aims to analyze the structure of four Aβ species in lipid membranes. These are the most abundant form of Aβ, Aβ1-40, and the more cytotoxic form, Aβ1-42, as well as their pyroglutamylated counterparts, pEAβ3-40 and pEAβ3-42, which are hypertoxic. These peptides have been studied using biophysical approaches, i.e., circular dichroism, fluorescence spectroscopy, and Fourier transform infrared spectroscopy. Elucidation of the structure of Aβ membrane pores provides valuable insight into the mechanism of Aβ toxicity and may help develop novel therapies for the lethal mystery that is AD.

Rous Sarcoma Virus (RSV) is an avian retrovirus with an enclosing capsid protein (CA) shell. RSV CA is studied due to its similar molecular structure to other retrovirus capsid proteins such as Human Immunodeficiency Virus (HIV). In this project, turbidity assay is used to track the assembly process of RSV CA, while solid state nuclear magnetic resonance (ssNMR) is used to probe the CA structure at a site specific level and investigate the morphology of the spherical structure of the I190V mutated strain of RSV CA. The I190V mutant is a naturally occurring mutation and is able to form into roughly uniform spheres, where the wild type RSV CA cannot form as pure spheres as possible. Turbidity assay results of the mutated RSV CA revealed a lack of a noticeable lag time before assembly began, as well as, a prolonged time period to reach saturation when compared to the wild-type RSV CA. Using ssNMR, and the TALOS-N program the torsion angles of the protein backbone were found. Using Ramachandran plots, it was found that the mutation of the 190th residue from Isoleucine to Valine caused a changed in the secondary structure of residues, from α-helix to β-sheet and vice versa. These changes were concentrated at the loops between select interfaces of helices that make up the structure of RSV CA. In particular, between helices 4 (residues 65-85), 8 (residues 165-177), and 11 (residues 215-225). The differing secondary structure in the mutant RSV CA was supported by the overlaying of the NMR spectra of the wild-type RSV CA on to the spherically assembled mutant RSV CA. It can be concluded that the spherical assembly of the mutated RSV CA displays noticeable differences in assembly and overall structure when compared to the wild-type RSV CA.

The development of organic-inorganic hybrid materials is of great interest in thermoelectrics for its potential to combine the desirable characteristics of both classes of materials. Thermoelectric materials must combine low thermal conductivity with high electrical conductivity, but in most materials, thermal and electrical conductivity are closely related and positively correlated. By combining the low thermal conductivity, flexibility, facile processing, and low cost of organic components with the high electrical conductivity and stability of inorganic components, materials with beneficial thermoelectric properties may be realized. Here, we describe the synthesis and characterization of anthracene-containing organic-inorganic hybrid materials for thermoelectric purposes. Specifically, POSS-ANT was synthesized when aminopropylisobutyl-POSS was functionalized with a single anthracene unit via DCC-mediated amide formation. Acrylate-POSS was functionalized with multiple anthracene units in a Heck coupling reaction to synthesize System 1. System 2 was developed through a two-step synthetic process. In the first reaction, (3- acryloxypropyl)methyl dimethyoxy silane was functionalized with anthracene at the 9- position through a Heck coupling reaction. The second reaction was a base-catalyzed solgel process to form polymeric nanoparticles. Finally, System 3 was synthesized through a similar process to System 2, though polymers formed in the initial step. The System 3 precursor was to be developed through a potassium carbonate-catalyzed ether synthesis from 3-(bromopropyl)trimethoxysilane and 9-anthracene methanol, followed by a basecatalyzed sol-gel process to form nanoparticles. The precursor was never isolated because of premature polymerization during the precursor synthesis step, and polymeric nanoparticles were obtained for System 3 during the sol-gel process. These materials were characterized by TEM to reveal the nanostructures that formed upon evaporation from solution. Future work will focus on the characterization of thermoelectric parameters and incorporation into thermoelectric devices.

The complexity of the interface between the muscular system and the nervous system is still elusive. We investigated how the neuromuscular system functions and how it is influenced by various perturbations. Postural stability was selected as the model system, because this system provides complex output, which could indicate underlying mechanisms and feedback loops of the neuromuscular system. We hypothesized that aging, physical pain, and mental and physical perturbations affect balancing strategy, and based on these observations, we constructed a model that simulates many aspects of the neuromuscular system. Our results show that aging changes the control strategy of balancing from more chaotic to more repetitive. The chaotic elements ensure quick reactions and strong capacity to compensate for the perturbations; this adeptly reactive state changes into a less reactive, slower, probably less mechanically costly balancing strategy. Mental tasks during balancing also decreased the chaotic elements in balancing strategy, especially if the subject experienced chronic pain. Additional motoric tasks, such as tying knots while balancing, were correlated with age but unaffected by chronic pain. Our model competently predicted the experimental findings, and we proceeded to use the model with an external data set from Physionet to predict the balancing strategy of Parkinson’s patients. Our neurological model, comprised of RLC circuits, provides a mechanistic explanation for the neuromuscular system adaptations.

Gas phase molecular clusters present an ideal medium for observing factors that drive chemical reactions without outside interferences from excessive solvent molecules. Introducing an ion into the cluster promotes ion-molecule interactions that may manifest in a variety of non-covalent or even covalent binding motifs and are of significant importance in many fields including atmospheric and astronomical sciences. For instance, in outer space, molecules are subject to ionizing radiation where ion-molecule reactions become increasingly competitive to molecule-molecule interactions. To elucidate individual ion-molecule interaction information, mass spectrometry was used in conjunction with appropriate theoretical calculations. Three main categories of experiment were conducted in this dissertation. The first of which were thermochemical equilibrium measurements where an ion was introduced to an ion mobility drift cell wherein thermalizing collisions occur with helium buffer gas facilitating a reversible reaction with a neutral molecule allowing the standard changes in enthalpy and entropy to be determined. The second type of experiment was an ion mobility experiment where an ionized homo- or hetero-cluster was injected into the drift cell at specific conditions allowing the reduced mobility and collisional cross-section to be evaluated. Thirdly, kinetics measurements were taken following injection of an ion into the drift cell were an irreversible reaction ensued with the neutral species hindering equilibrium, but prompting rate constant assessment. Previous research has laid the groundwork for this dissertation as the results and discussion contained herein will build upon existing data while maintaining originality. For example, past work has given support for ion-molecule reactions involving precursor species such as acetylene and hydrogen cyanide to form more complex organics, perhaps leading to biologically relevant species. The chemical systems studied for this research are either ionized substituted benzenes like phenylacetylene and benzonitrile or polycyclic aromatic nitrogen-containing hydrocarbons like quinoline and quinoxaline interacting with a variety of neutral species. Hydrogen bonding and its many sub-sections are of the utmost importance to the kinds of reactions studied here. Past work has shown the tendency of organic radical cations to form conventional and unconventional ionic hydrogen bonds with gas phase solvents. Other non-covalent modes of interaction have also been detected in addition to the formation of covalently bound species. Gas phase reactions studied here will explore, via mass-selected ion mobility, reversible and irreversible reactions leading to binding enthalpy and entropy and rate constant determination, respectively, in addition to collisional cross-section determination.

The methods that fueled the microscale revolution (top-down design/fabrication, combined with application of forces large enough to overpower stochasticity) constitute an approach that will not scale down to nanoscale systems. In contrast, in nanotechnology, we strive to embrace nature’s quite different paradigms to create functional systems, such as self-assembly to create structures, exploiting stochasticity, rather than overwhelming it, in order to create deterministic, yet highly adaptable, behavior. Nature’s approach, through billions of years of evolutionary development, has achieved self-assembling, self-duplicating, self-healing, adaptive systems. Compared to microprocessors, nature’s approach has achieved eight orders of magnitude higher memory density and three orders of magnitude higher computing capacity while utilizing eight orders of magnitude less power. Perhaps the most complex of functions, homeostatis by a biological cell – i.e., the regulation of its internal environment to maintain stability and function – in a fluctuating and unpredictable environment, emerges from the interactions between perhaps 50M molecules of a few thousand different types. Many of these molecules (e.g. proteins, RNA) are produced in the stochastic processes of gene expression, and the resulting populations of these molecules are distributed across a range of values. So although homeostasis is maintained at the system (i.e. cell) level, there are considerable and unavoidable fluctuations at the component (protein, RNA) level. While on at least some level, we understand the variability in individual components, we have no understanding of how to integrate these fluctuating components together to achieve complex function at the system level. This thesis will explore the regulation and control of stochasticity in cells. In particular, the focus will be on (1) how genetic circuits use noise to generate more function in less space; (2) how stochastic and deterministic responses are co-regulated to enhance function at a system level; and (3) the development of high-throughput analytical techniques that enable a comprehensive view of the structure and distribution of noise on a whole organism level.