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Identification Of Proteins Involved In Cell Membrane Permeabilization By Nanosecond Electric Pulses (Nsep), Giedre Silkuniene, Uma Mangalanathan, Alessandra Rossi, Peter A. Mollica, Andrei G. Pakhomov, Olga N. Pakhomova
Identification Of Proteins Involved In Cell Membrane Permeabilization By Nanosecond Electric Pulses (Nsep), Giedre Silkuniene, Uma Mangalanathan, Alessandra Rossi, Peter A. Mollica, Andrei G. Pakhomov, Olga N. Pakhomova
Bioelectrics Publications
The study was aimed at identifying endogenous proteins which assist or impede the permeabilized state in the cell membrane disrupted by nsEP (20 or 40 pulses, 300 ns width, 7 kV/cm). We employed a LentiArray CRISPR library to generate knockouts (KOs) of 316 genes encoding for membrane proteins in U937 human monocytes stably expressing Cas9 nuclease. The extent of membrane permeabilization by nsEP was measured by the uptake of Yo-Pro-1 (YP) dye and compared to sham-exposed KOs and control cells transduced with a non-targeting (scrambled) gRNA. Only two KOs, for SCNN1A and CLCA1 genes, showed a statistically significant reduction in …
Nanosecond Pulsed Electric Signals Can Affect Electrostatic Environment Of Protiens Below The Threshold Of Conformational Effects: The Case Study Of Sod1 With A Molecular Simulation Study, Elena Della Valle, Paolo Marracino, Olga Pakhomova, Micaela Liberti, Francesca Apollonio
Nanosecond Pulsed Electric Signals Can Affect Electrostatic Environment Of Protiens Below The Threshold Of Conformational Effects: The Case Study Of Sod1 With A Molecular Simulation Study, Elena Della Valle, Paolo Marracino, Olga Pakhomova, Micaela Liberti, Francesca Apollonio
Bioelectrics Publications
Electric fields can be a powerful tool to interact with enzymes or proteins, with an intriguing perspective to allow protein manipulation. Recently, researchers have focused the interest on intracellular enzyme modifications triggered by the application of nanosecond pulsed electric fields. These findings were also supported by theoretical predictions from molecular dynamics simulations focussing on significant variations in protein secondary structures. In this work, a theoretical study utilizing molecular dynamics simulations is proposed to explore effects of electric fields of high intensity and very short nanosecond duration applied to the superoxide dismutase (Cu/Zn-SOD or SOD-1), an important enzyme involved in the …
Effects Of Anchor Structure And Glycosylation Of Fcî³ Receptor Iii On Ligand Binding Affinity, Ning Jiang, Wei Chen, Prithiviraj Jothikumar, Jaina M. Patel, Rangaiah Shashidharamurthy, Periasamy Selvaraj, Cheng Zhu
Effects Of Anchor Structure And Glycosylation Of Fcî³ Receptor Iii On Ligand Binding Affinity, Ning Jiang, Wei Chen, Prithiviraj Jothikumar, Jaina M. Patel, Rangaiah Shashidharamurthy, Periasamy Selvaraj, Cheng Zhu
PCOM Scholarly Papers
Isoforms of the Fcγ receptor III (FcγRIII or CD16) are cell surface receptors for the Fc portion of IgG and important regulators of humoral immune responses. Different ligand binding kinetics of FcγRIII isoforms are obtained in three dimensions by surface plasmon resonance and in two dimensions by a micropipette adhesion frequency assay. We show that the anchor structure of CD16 isoforms isolated from the cell membrane affects their binding affinities in a ligand-specific manner. Changing the receptor anchor structure from full to partial to none decreases the ligand binding affinity for human IgG1 (hIgG1) but increases it for murine IgG2a …
Activating The Msh2/Msh6 Apoptotic Pathway In Cancer Cells Using Non-Reserpine Compounds, Jacob M. Mauceri
Activating The Msh2/Msh6 Apoptotic Pathway In Cancer Cells Using Non-Reserpine Compounds, Jacob M. Mauceri
Honors College Theses
DNA mismatch repair (MMR) is a system that is highly conserved in both prokaryotes and eukaryotes. The heterodimeric protein MutSα and a suite of associated proteins are essential in the recognition and repair of DNA afflicted with mispaired bases and short insertion/deletion loops, but are also implicated in funneling damaged cells towards apoptosis via a key conformational change in a subunit of the MutSα complex. This conformation can be bound specifically by the small molecule reserpine. Molecular dynamics modeling and virtual screening were used to identify additional small molecule novel ligands with the predicted ability to selectively bind this “death” …
Picosecond To Terahertz Perturbation Of Interfacial Water And Electropermeabilization Of Biological Membranes, P. Thomas Vernier, Zachary A. Levine, Ming-Chak Ho, Shu Xiao, Iurii Semenov, Andrei G. Pakhomov
Picosecond To Terahertz Perturbation Of Interfacial Water And Electropermeabilization Of Biological Membranes, P. Thomas Vernier, Zachary A. Levine, Ming-Chak Ho, Shu Xiao, Iurii Semenov, Andrei G. Pakhomov
Bioelectrics Publications
Non-thermal probing and stimulation with subnanosecond electric pulses and terahertz electromagnetic radiation may lead to new, minimally invasive diagnostic and therapeutic procedures and to methods for remote monitoring and analysis of biological systems, including plants, animals, and humans. To effectively engineer these still-emerging tools, we need an understanding of the biophysical mechanisms underlying the responses that have been reported to these novel stimuli. We show here that subnanosecond (≤500 ps) electric pulses induce action potentials in neurons and cause calcium transients in neuroblastoma-glioma hybrid cells, and we report complementary molecular dynamics simulations of phospholipid bilayers in electric fields in which …
Tracing Beta Strands Using Strandtwister From Cryo-Em Density Maps At Medium Resolutions, Dong Si, Jing He
Tracing Beta Strands Using Strandtwister From Cryo-Em Density Maps At Medium Resolutions, Dong Si, Jing He
Computer Science Faculty Publications
Major secondary structure elements such as α helices and β sheets can be computationally detected from cryoelectron microscopy (cryo-EM) density maps with medium resolutions of 5–10 A˚ . However, a critical piece of information for modeling atomic structures is missing, because there are no tools to detect β strands from cryo-EM maps at medium resolutions. We propose a method, StrandTwister, to detect the traces of β strands through the analysis of twist, an intrinsic nature of a β sheet. StrandTwister has been tested using 100 β sheets simulated at 10 A˚ resolution and 39 β sheets computationally detected from cryo-EM …