Browsing by Author "Petrache, Horia I."
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Item 1H NMR of Deep Eutectic Solvents(Office of the Vice Chancellor for Research, 2014-04-11) Wallis, J. Lincoln; Sapir, Liel; Harries, Daniel; Petrache, Horia I.; Ray, Bruce D.Deep Eutectic Solvents (DESs) form between a variety of quaternary ammonium or phosphonium salts and hydrogen-bond donors. Over the past decade, DESs have been studied as green solvents with potential applications in industrial processes, chemical extractions, and pharmaceuticals. The recent suggestion that many plants produce natural deep eutectic solvents (NADES) from primary metabolites led to investigation of the potential uses of DESs in biophysics research. This study examined the 1H NMR spectra of the choline chloride:urea 1:2, and choline chloride:ethylene glycol 1:3 molar ratio DES. Spectra of the choline chloride:urea 1:2 with various solutes were acquired to see what effect these solutes had on the DESs NMR spectrum. For both DESs tested, the NMR spectra were a superposition of the spectra of the components. DES-solute spectra showed that interaction between components persisted, indicating the solvent properties of the DESs were not lost upon addition of solutes.Item 3D Printing of Human Ossicle Models for the Biofabrication of Personalized Middle Ear Prostheses(MDPI, 2022-10-31) Dairaghi, Jacob; Rogozea, Dan; Cadle, Rachel; Bustamante, Joseph; Moldovan, Leni; Petrache, Horia I.; Moldovan, Nicanor I.; Physics, School of ScienceThe middle ear bones (‘ossicles’) may become severely damaged due to accidents or to diseases. In these situations, the most common current treatments include replacing them with cadaver-derived ossicles, using a metal (usually titanium) prosthesis, or introducing bridges made of biocompatible ceramics. Neither of these solutions is ideal, due to the difficulty in finding or producing shape-matching replacements. However, the advent of additive manufacturing applications to biomedical problems has created the possibility of 3D-printing anatomically correct, shape- and size-personalized ossicle prostheses. To demonstrate this concept, we generated and printed several models of ossicles, as solid, porous, or soft material structures. These models were first printed with a plottable calcium phosphate/hydroxyapatite paste by extrusion on a solid support or embedded in a Carbopol hydrogel bath, followed by temperature-induced hardening. We then also printed an ossicle model with this ceramic in a porous format, followed by loading and crosslinking an alginate hydrogel within the pores, which was validated by microCT imaging. Finally, ossicle models were printed using alginate as well as a cell-containing nanocellulose-based bioink, within the supporting hydrogel bath. In selected cases, the devised workflow and the printouts were tested for repeatability. In conclusion, we demonstrate that moving beyond simplistic geometric bridges to anatomically realistic constructs is possible by 3D printing with various biocompatible materials and hydrogels, thus opening the way towards the in vitro generation of personalized middle ear prostheses for implantation.Item ANALYSIS OF MULTICHANNEL SIGNALS USING A CHANNEL SIMULATOR(Office of the Vice Chancellor for Research, 2012-04-13) Palacio, Luis A.; Petrache, Horia I.In biological systems ion channels can be thought of as opening and clos-ing pores that allow the flow of ion through a membrane. Ion channels are responsible for intracellular communication and keeping an osmotic equilib-rium across cell membranes. Measurements of ion channel activities that generate multichannel events (the opening of more than one channel at a time) are important to understand, but difficult to analyze. In many cases the multichannel events are discarded instead of used in the analysis. The availability of a channel signal simulator offers an excellent opportunity to develop and test statistical models for analysis of multichannel signals. We have generated single channel traces for various open probabilities and then digitally superimposed these signals to obtain multichannel events. We then applied our simplified analysis to these multichannel traces to calculate sin-gle channel parameters such as the average ON and OFF times and their statistical distribution of the ON times. The average ON time as well as the ON time distribution matched the single channel input mean open time. The importance of our findings is that our proposed analysis will be able to use the statistical distribution of ON times, in addition to the traditional “dwell time” (or average ON time) parameter, to characterize ion channels.Item Beyond the Exceptional Point: Exploring the Features of Non-Hermitian PT Symmetric Systems(2022-08) Agarwal, Kaustubh Shrikant; Joglekar, Yogesh N.; Vemuri, Gautam; Ou, Zhe “Jeff”; Petrache, Horia I.; Lukens, Joseph M.Over the past two decades, open systems that are described by a non-Hermitian Hamiltonian have become a subject of intense research. These systems encompass classical wave systems with balanced gain and loss, semi-classical models with mode selective losses, and lossy quantum systems. The rapidly growing research on these systems has mainly focused on the wide range of novel functionalities they demonstrate. In this thesis, I intend to present some intriguing properties of a class of open systems which possess parity (P) and time-reversal (T) symmetry with a theoretical background, accompanied by the experimental platform these are realized on. These systems show distinct regions of broken and unbroken symmetries separated by a special phase boundary in the parameter space. This separating boundary is called the PT-breaking threshold or the PT transition threshold. We investigate non-Hermitian systems in two settings: tight binding lattice models, and electrical circuits, with the help of theoretical and numerical techniques. With lattice models, we explore the PT-symmetry breaking threshold in discrete realizations of systems with balanced gain and loss which is determined by the effective coupling between the gain and loss sites. In one-dimensional chains, this threshold is maximum when the two sites are closest to each other or the farthest. We investigate the fate of this threshold in the presence of parallel, strongly coupled, Hermitian (neutral) chains, and find that it is increased by a factor proportional to the number of neutral chains. These results provide a surprising way to engineer the PT threshold in experimentally accessible samples. In another example, we investigate the PT-threshold for a one-dimensional, finite Kitaev chain—a prototype for a p-wave superconductor— in the presence of a single pair of gain and loss potentials as a function of the superconducting order parameter, onsite potential, and the distance between the gain and loss sites. In addition to a robust, non-local threshold, we find a rich phase diagram for the threshold that can be qualitatively understood in terms of the band-structure of the Hermitian Kitaev model. Finally, with electrical circuits, we propose a protocol to study the properties of a PT-symmetric system in a single LC oscillator circuit which is contrary to the notion that these systems require a pair of spatially separated balanced gain and loss elements. With a dynamically tunable LC oscillator with synthetically constructed circuit elements, we demonstrate static and Floquet PT breaking transitions by tracking the energy of the circuit. Distinct from traditional mechanisms to implement gain and loss, our protocol enables parity-time symmetry in a minimal classical system.Item Cation-selective channel is regulated by anions according to their Hofmeister ranking(Wiley, 2017-03-20) Gurnev, Philip A.; Roark, Torri C.; Petrache, Horia I.; Sodt, Alexander J.; Bezrukov, Sergey M.; Physics, School of ScienceSpecificity of small ions, the Hofmeister ranking, is long-known and has many applications including medicine. Yet it evades consistent theoretical description. Here we study the effect of Hofmeister anions on gramicidin A channels in lipid membranes. Counterintuitively, we find that conductance of this perfectly cation-selective channel increases about two-fold in the H2PO4−Item Collaborative Research from the Center for Membrane Biosciences(Office of the Vice Chancellor for Research, 2010-04-09) Petrache, Horia I.; Justice, Matthew J.; Rogozea, Adriana L.; Patrusca, Daniela N.; Petrache, Irina; Wassall, Stephen R.; Siegel, Amanda; Murcia, Mike; Minner, Dan; Elmendorf, Jeffrey S.; Tackett, Lixuan; Naumann, Christoph A.The Center for Membrane Biosciences has been facilitating new research activities between the IUPUI School of Science and IU School of Medicine in the structure, biochemistry, and physiology of biological membranes. Results from two projects resulting from these collaborations are presented. Project 1: Ceramides are sphingolipids involved in the development of lung alveolar cell apoptosis (programmed death) and possibly in the clearance of apoptotic cells by alveolar macrophages. We use a combination of molecular and cellular methods to determine the effect of ceramides on the ability of alveolar macrophages to engulf apoptotic cells. Engulfment experiments of labeled apoptotic Jurkat cells were performed with rat alveolar macrophages (AM) obtained via bronchoalveolar lavage. AM were treated with various ceramide species and efferocytosis was quantified by flow cytometry. Using small-angle X-ray scattering and solid state 2H NMR we determined how ceramides (C6:0, C18:1) affect the molecular organization and the physical properties of model membranes. These studies can lead to a better understanding of the molecular mechanisms responsible for apoptotic cell clearance. If the clearance process is impaired, apoptotic cells may progress to secondary necrosis, resulting in release of harmful cellular contents and tissue inflammation. Project 2: Highly-photostable quantum dots (QD) conjugated to lipids or antibodies can be utilized to explore changes in compartmentalization of the plasma membrane due to hyperinsulinemia using wide field single molecule fluorescence microscopy. Protocols describing the bio-inertness and monovalent binding of QDs to antibodies are outlined, as well as use of confocal fluorescence correlation spectroscopy to determine colloidal stability of CdSe/ZnS QDs in aqueous solution. Tracking experiments on QD-conjugated to transferrin receptors in healthy and insulin-resistant adipocytes detect changes in membrane compartmentalization. The impact of chromium picolinate on receptor mobility was also investigated.Item Conductance of Ideally Cation Selective Channel Depends on Anion Type(Office of the Vice Chancellor for Research, 2013-04-05) Roark, Torri C.; Gurnev, Philip A.; Petrache, Horia I.; Bezrukov, Sergey M.Gramicidin A (gA) is a transmembrane, cation selective ion channel that has been used in many biophysical studies of lipid bilayers, in particular for investigations of lipid-protein interactions and membrane electrostatics. In addition, it was found that ionic interactions with neutral lipid membranes also affect the kinetics of gA channels. Here we report measurements of gA ion-channels for a series of sodium and potassium salts that show an anion-dependence of gA conductance. We find that gA conductance varies significantly with the anion type with ClO4 and SCN producing distinctly larger conductance values than Cl, F, and H2PO4. These results can provide new insights into ion-lipid membrane interactions and ion channel functions in general.Item Correlations of Specific Ionic Effects using Ion Channels and Surface Charge Measurements(Office of the Vice Chancellor for Research, 2014-04-11) Roark, Torri C.; Hermida, Oscar Teijido; Rostovtseva, Tatiana K.; Gurnev, Philip A.; Petrache, Horia I.; Bezrukov, Sergey M.Specific ionic effects, as captured in the Hofmeister series, have been observed in many biological phenomena including protein folding and aggregation and lipid bilayer interactions. Previously we have shown that the Hofmeister effect is present in the activity of gramicidin A channels. In particular, measurements of channel open lifetime and conductance in potassium salts clearly show the existence of two distinct ionic classes that could be identified as kosmotropic and chaotropic. To further investigate this behavior, we have measured the zeta potential of diphytanoyl phosphatidylcholine (DPhPC) liposomes in salt solutions. We observe that anions alter the surface charge of the liposomes depending on the classification of the anion as kosmotropic or chaotropic. Chaotropic anions (SCN-, ClO4-) decrease the surface charge of the liposomes while kosmotropic anions (Cl-, H2PO4-, SO42-) have the opposite effect. These results correlate with our previous studies of cation conductance through gramicidin A channels adding new insight into ionic interactions at the lipid-water interface.Item Detecting Counterfeit Pharmaceuticals through UV Spectrophotometry(Office of the Vice Chancellor for Research, 2015-04-17) Figueroa, Gabriela; Palacio, Luis A.; Ray, Bruce D.; Petrache, Horia I.; Lopez-Yunez, AlfredoAccording to the World Health Organization between 10%-30% of medicines, in Africa, Asia and South America, are counterfeit or sub-standard, affecting the health of millions of people. Currently, there is no effective way to check the quality of a medicine at the point of care, leaving many with treatable diseases at risk. The goal of this study is to identify UV-Vis (240nm - 500nm) absorbance patterns that would indicate if a drug is sub-standard or counterfeit. UV-Vis spectroscopy was selected as the method for testing due to the maturity and availability of the technology. Pure Acetaminophen and Tylenol were used as controls for proof of concept. Samples were prepared by dissolving different combinations of the pure active ingredient and adulterants such as cement, rice flour, vitamin C and lactose in three different types of solvents (H2O, 0.1 M HCl, 0.1 NaOH). Various concentrations (ranging from 0.01mg/ml to 0.04mg/ml) and mixing ratios were analyzed using a UV-Vis Spectrophotometer. It was found that adulterants significantly decrease the absorption of acetaminophen at 245nm by interacting with its benzene ring, while showing a slight increase in other parts of the spectrum. UV-Vis scans show that the amount of change in absorbance at specific wavelengths, coupled with characteristic wavelength shifts produced by different solvents, can be used for detection of counterfeit drugs. The methods presented here could be used for quality control of medicines at or near the point of care in parts of the world at higher risk of encountering defective pharmaceuticals.Item Direct affinity of dopamine to lipid membranes investigated by Nuclear Magnetic Resonance spectroscopy(Elsevier, 2016-04) Matam, Yashasvi; Ray, Bruce D.; Petrache, Horia I.; Department of Physics, School of ScienceDopamine, a naturally occurring neurotransmitter, plays an important role in the brain’s reward system and acts on sensory receptors in the brain. Neurotransmitters are contained in lipid membraned vesicles and are released by exocytosis. All neurotransmitters interact with transport and receptor proteins in glial cells, on neuronal dendrites, and at the axonal button, and also must interact with membrane lipids. However, the extent of direct interaction between lipid membranes in the absence of receptors and transport proteins has not been extensively investigated. In this report, we use UV and NMR spectroscopy to determine the affinity and the orientation of dopamine interacting with lipid vesicles made of either phosphatidylcholine (PC) or phosphatidylserine (PS) lipids which are primary lipid components of synaptic vesicles. We quantify the interaction of dopamine's aromatic ring with lipid membranes using our newly developed method that involves reference spectra in hydrophobic environments. Our measurements show that dopamine interacts with lipid membranes primarily through the aromatic side opposite to the hydroxyl groups, with this aromatic side penetrating deeper into the hydrophobic region of the membrane. Since dopamine's activity involves its release into extracellular space, we have used our method to also investigate dopamine's release from lipid vesicles. We find that dopamine trapped inside PC and PS vesicles is released into the external solution despite its affinity to membranes. This result suggests that dopamine's interaction with lipid membranes is complex and involves both binding as well as permeation through lipid bilayers, a combination that could be an effective trigger for apoptosis of dopamine-generating cells.