Electrostatic Switch Research Articles

Thick membrane operated rf microelectromechanical system switch with low actuation voltage

Most researcher who have studied the radio frequency (rf) microelectromechanical system (MEMS) switch has focused on the electrostatic actuation types switch because of this type’s low power consumption, simple fabrication method, and good rf characteristics compared to magnetic, thermal, and piezoelectric driving method. However, most of electrostatic actuation type switch needs high operation voltage compared to other types. One of the reasons that affect the high operation voltage is the bending of the membrane because of an internal stress gradient. This bending increases the gap between electrode and membrane. To solve this problem, the authors developed the thick membrane operated seesaw type rf MEMS switch. This membrane consisted of a pivot under single crystal thick silicon membrane for a seesaw mode operation and a flexible spring for an up-down actuation mode. After the fabrication of this switch, the authors measured its rf characteristics. The minimum actuation voltage was about 12V, the isol...

Row/Column Addressing Scheme for Large Electrostatic Actuator MEMS Switch Arrays and Optimization of the Operational Reliability by Statistical Analysis

This paper investigates the design and optimization of a row/column addressing scheme to individually pull in or pull out single electrostatic actuators in an N2 array, utilizing the electromechanical hysteresis behavior of electrostatic actuators and efficiently reducing the number of necessary control lines from N2 complexity to 27 V. This paper illustrates the principle of the row/column addressing scheme. Furthermore, it investigates the optimal addressing voltages to individually pull in or pull out single actuators with maximum operational reliability, determined by the statistical parameters of the pull-in and pull-out characteristics of the actuators. The investigated addressing scheme is implemented for the individual addressing of cross-connect switches in a microelectromechanical systems 20 X 20 switch array, which is utilized for the automated any-to-any interconnection of 20 input signal line pairs to 20 output signal line pairs. The investigated addressing scheme and the presented calculations were successfully tested on electrostatic actuators in a fabricated 20 X 20 array. The actuation voltages and their statistical variations were characterized for different subarray cluster sizes. Finally, the addressing voltages were calculated and verified by tests, resulting in an operational reliability of 99.9498% (502 parts per million (ppm) failure rate) for a 20 X 20 switch array and of 99.99982% (1.75 ppm failure rate) for a 3 X 3 subarray cluster. The array operates by AC-actuation voltage to minimize the disturbing effects by dielectric charging of the actuator isolation layers, as observed in this paper for DC-actuation voltages.

Structural Basis for Ca2+-Dependent Formation of ALG-2/Alix Peptide Complex: Ca2+/EF3-Driven Arginine Switch Mechanism

ALG-2 belongs to the penta-EF-hand (PEF) protein family and interacts with various intracellular proteins, such as Alix and TSG101, that are involved in endosomal sorting and HIV budding. Through X-ray crystallography, we solved the structures of Ca(2+)-free and -bound forms of N-terminally truncated human ALG-2 (des3-20ALG-2), Zn(2+)-bound form of full-length ALG-2, and the structure of the complex between des3-23ALG-2 and the peptide corresponding to Alix799-814 in Zn(2+)-bound form. Binding of Ca(2+) to EF3 enables the side chain of Arg125, present in the loop connecting EF3 and EF4, to move enough to make a primary hydrophobic pocket accessible to the critical PPYP motif, which partially overlaps with the GPP motif for the binding of Cep55 (centrosome protein 55 kDa). Based on these results, together with the results of in vitro binding assay with mutant ALG-2 and Alix proteins, we propose a Ca(2+)/EF3-driven arginine switch mechanism for ALG-2 binding to Alix.

The “Electrostatic-Switch” Mechanism: Monte Carlo Study of MARCKS-Membrane Interaction

The binding of the myristoylated alanine-rich C kinase substrate (MARCKS) to mixed, fluid, phospholipid membranes is modeled with a recently developed Monte Carlo simulation scheme. The central domain of MARCKS is both basic ( ζ = +13) and hydrophobic (five Phe residues), and is flanked with two long chains, one ending with the myristoylated N-terminus. This natively unfolded protein is modeled as a flexible chain of “beads” representing the amino acid residues. The membranes contain neutral ( ζ = 0), monovalent ( ζ = −1), and tetravalent ( ζ = −4) lipids, all of which are laterally mobile. MARCKS-membrane interaction is modeled by Debye-Hückel electrostatic potentials and semiempirical hydrophobic energies. In agreement with experiment, we find that membrane binding is mediated by electrostatic attraction of the basic domain to acidic lipids and membrane penetration of its hydrophobic moieties. The binding is opposed by configurational entropy losses and electrostatic membrane repulsion of the two long chains, and by lipid demixing upon adsorption. The simulations provide a physical model for how membrane-adsorbed MARCKS attracts several PIP 2 lipids ( ζ = −4) to its vicinity, and how phosphorylation of the central domain ( ζ = +13 to ζ = +7) triggers an “electrostatic switch”, which weakens both the membrane interaction and PIP 2 sequestration. This scheme captures the essence of “discreteness of charge” at membrane surfaces and can examine the formation of membrane-mediated multicomponent macromolecular complexes that function in many cellular processes.

Solving functional reliability issue for an optical electrostatic switch

In this paper, we report the advantage of using AC actuating signal for driving micro electro mechanical systems actuators instead of DC voltages. The study is based upon micro mirror devices used in digital mode for optical switching operation. When the pull-in effect is used, charge injection occurs when the micro mirror is maintained in the deflected position. To avoid this effect, a geometrical solution is to realize grounded landing electrodes which are electro-statically separated from the control electrodes. Another solution is the use of AC signal which eliminates charge injection particularly if a bipolar signal is used. Long-term experiments have demonstrated the reliability of such a signal command to avoid injection of electric charges.

Optocoupler driving of MEMS electrostatic switches

The dynamics of novel optocoupler direct driving of a microelectromechanical systems (MEMS) switch is described by means of PSpice simulations and experimental measurements. The output circuit of an optocoupler array is used to drive an electrostatic MEMS switch. It is shown that the optocoupler drive provides built-in dc voltage step-up conversion with no ripple, galvanic isolation and switching time and energy control in a similar way as current drive does. PSpice models describe the actuation theory including parasitic elements, which can modify the actuation characteristics. Comparison between theory and measurements shows that although there is great impact of parasitic parallel resistance and capacitance, current drive benefits are mostly preserved.

Off-line ion source terminal for ISAC at TRIUMF

The off-line ion source (OLIS) terminal consists of a microwave cusp ion source, either a surface ion source or a hybrid surface-arc discharge ion source and an electrostatic switch that allows selecting any one of the sources without mechanical intervention. These sources provide variety of beams to ISAC experiments, for commissioning the accelerators, for setting up the radioactive experiments, and for tuning the beam lines. The microwave ion source has been operational since 1995 and provides singly and doubly charged beams from various stable isotopes for many ISAC experiments at high and low energy areas. Originally its prime goal was to provide beams from gaseous elements, but later two ovens and a sputtering system were added in order to provide beams from liquids and from solids. The surface ion source installed in 2002 can provide low energy spread beams from alkali and semialkali elements. It also has three separate ovens and an ionizer. Therefore, it can provide three different temperature regions simultaneously to provide different beams to ISAC. It is mainly used for laser spectroscopy experiments and other experiments, which require a finite beam quality. A hybrid surface-arc discharge ion source was also developed and installed in order to meet specific demands from experiments. This source terminal is now automated for start up and for mass selection. It is capable of providing stable beams for months without maintenance and it is also capable of providing negative ion beams if required. To date, over 40 different isotopes including many rear isotopes were delivered to various experiments from the OLIS source terminal. Performances of the ion sources and some of the results are discussed.

Mechanistic Basis of Differential Cellular Responses of Phosphatidylinositol 3,4-Bisphosphate- and Phosphatidylinositol 3,4,5-Trisphosphate-binding Pleckstrin Homology Domains

Phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) are lipid second messengers that regulate various cellular processes by recruiting a wide range of downstream effector proteins to membranes. Several pleckstrin homology (PH) domains have been reported to interact with PtdIns(3,4)P2 and PtdIns(3,4,5)P3. To understand how these PH domains differentially respond to PtdIns(3,4)P2 and PtdIns(3,4,5)P3 signals, we quantitatively determined the PtdIns(3,4)P2 and PtdIns(3,4,5)P3 binding properties of several PH domains, including Akt, ARNO, Btk, DAPP1, Grp1, and C-terminal TAPP1 PH domains by surface plasmon resonance and monolayer penetration analyses. The measurements revealed that these PH domains have significant different phosphoinositide specificities and affinities. Btk-PH and TAPP1-PH showed genuine PtdIns(3,4,5)P3 and PtdIns(3,4)P2 specificities, respectively, whereas other PH domains exhibited less pronounced specificities. Also, the PH domains showed different degrees of membrane penetration, which greatly affected the kinetics of their membrane dissociation. Mutational studies showed that the presence of two proximal hydrophobic residues on the membrane-binding surface of the PH domain is important for membrane penetration and sustained membrane residence. When NIH 3T3 cells were stimulated with platelet-derived growth factor to generate PtdIns(3,4,5)P3, reversible translocation of Btk-PH, Grp1-PH, ARNO-PH, DAPP1-PH, and its L177A mutant to the plasma membrane was consistent with their in vitro membrane binding properties. Collectively, these studies provide new insight into how various PH domains would differentially respond to cellular PtdIns(3,4)P2 and PtdIns(3,4,5)P3 signals.

See-saw Type RF MEMS Switch with Narrow Gap Vertical Comb

This paper presents the see-saw type RF MEMS switch based on a single crystalline silicon structure with narrow gap vertical comb. Low actuation voltage and high isolation are key features to be solved in electrostatic RF MEMS switch design. Since these parameters in conventional parallel plate RF MEMS switch designs are in trade-off relationship, both requirements cannot be met simultaneously. In the vertical comb design, however, the actuation voltage is independent of the vertical separation distance between the contact electrodes. Therefore, the large separation gap between contact electrodes is implemented to achieve high isolation. We have designed and fabricated RF MEMS switch which has 46dB isolation at 5GHz, 0.9dB insertion loss at 5GHz and 40V actuation voltage.

Lipid signaling and the modulation of surface charge during phagocytosis

Phagocytosis is an important component of innate and adaptive immunity. The formation of phagosomes and the subsequent maturation that capacitates them for pathogen elimination and antigen presentation are complex processes that involve signal transduction, cytoskeletal reorganization, and membrane remodeling. Lipids are increasingly appreciated to play a crucial role in these events. Sphingolipids, cholesterol, and glycerophospholipids, notably the phosphoinositides, are required for the segregation of signaling microdomains and for the generation of second messengers. They are also instrumental in the remodeling of the actin cytoskeleton and in directing membrane traffic. They accomplish these feats by congregating into liquid-ordered domains, by generating active metabolites that activate receptors, and by recruiting and anchoring specific protein ligands to the membrane, often altering their conformation and catalytic activity. A less appreciated role of acidic phospholipids is their contribution to the negative surface charge of the inner leaflet of the plasmalemma. The unique negativity of the inner aspect of the plasma membrane serves to attract and anchor key signaling and effector molecules that are required to initiate phagosome formation. Conversely, the loss of charge that accompanies phospholipid metabolism as phagosomes seal facilitates the dissociation of proteins and the termination of signaling and cytoskeleton assembly. In this manner, lipids provide a binary electrostatic switch to control phagocytosis.

The disassembly, reassembly and stability of CCMV protein capsids

Efficient procedures are described for the disassembly of Cowpea Chlorotic Mottle Virus (CCMV) into its viral-RNA and capsid-protein components, the separation of the RNA and protein, and the reassembly of the purified protein into higher order nanoscale structures. These straightforward biochemical techniques result in high yield quantities of protein suitable for further biophysical studies (AFM, X-ray scattering, NMR, osmotic stress experiments, protein phase-diagram) and nanotechnology applications (protein enclosed nanoparticles, protein-lipid nanoemulsion droplets). Also discussed are solution conditions that affect the stability of the self-assembled protein structure and explicitly show that divalent cation is not required to obtain stable protein structures, while the presence of even small amounts of Ba 2+ have a significant impact on protein self-assembly. However, since high ionic strength solution conditions result in good yields of CCMV-like protein capsids, it is suggested that the highly charged cationic protein N-terminus could act as an electrostatic switch for protein self-assembly and therefore be modulated by ionic strength and salt type. It was also found that CaCl 2/RNA precipitation methods do not yield sufficiently pure protein samples.

Definition of an electrostatic relay switch critical for the cAMP‐dependent activation of protein kinase A as revealed by the D170A mutant of RIα

The Regulatory (R) subunit of Protein Kinase A (PKA) inhibits its kinase activity by shielding the Catalytic (C) subunit from physiological substrates. This inhibition is reversed in response to extra-cellular signals that increase cAMP levels in the cytoplasm. Upon cAMP binding to R, C is allosterically released from R, activating a spectrum of downstream signaling cascades. Crystallographic data indicated that a series of distinct conformational changes within CBD-A must occur to relay the cAMP signal from the cAMP binding site to the R:C interaction interface. One critical cAMP relay site within the CBD-A of R has been identified as Asp170 because the D170A mutation selectively reduces the negative cooperativity between the cAMP- and C-recognition sites (i.e. the KD for the R:C complex in the presence of cAMP is reduced by more than 12-fold), without significantly compromising the high affinity of R for both binding partners. Here, utilizing an integrated set of comparative NMR analyses we have elucidated how this critical electrostatic switch is able to control the interaction network which transmits the cAMP signal within CBD-A. The D170A-induced variations in backbone chemical shifts as well as in hydrogen-deuterium and hydrogen-hydrogen exchange profiles show that Asp170 not only plays a pivotal role in controlling the local conformation of the phosphate binding cassette (PBC), where cAMP docks, but also significantly affects the long-range cAMP-dependent interaction network that extends from the PBC to the three major sites of C-recognition. We also found that the D170A mutation promotes partial unfolding, thus assisting the uncoupling of the alpha- and beta-subdomains of CBD-A as required for the major alpha-helical conformational re-arrangement necessary for C-binding. Overall, the emerging map of allosteric networks features Asp170 as an essential component of an electrostatic switch mechanism that stabilizes the conformation of the PBC region for optimal interaction with cAMP and that is also crucial for relaying allosteric effects leading to C subunit activation. Taken together, our results consolidate the interdependence between the Asp170 relay site and the R:C interaction interface. Furthermore, they provide insight into the driving forces for the in vivo formation of intermediate PKA ternary complexes. Finally, our current study is relevant for elucidating the antagonistic properties of Rp-cAMPS on PKA by providing a detailed picture of the long-range effects of the altered interaction between this analog and the PBC.

Dual substrate electrostatic MEMS switch with hermetic seal

Dual substrate electrostatic MEMS switch with hermetic seal

Plasma Membrane and Nuclear Localization of G Protein–coupled Receptor Kinase 6A

G protein-coupled receptor (GPCR) kinases (GRKs) specifically phosphorylate agonist-occupied GPCRs at the inner surface of the plasma membrane (PM), leading to receptor desensitization. Here we show that the C-terminal 30 amino acids of GRK6A contain multiple elements that either promote or inhibit PM localization. Disruption of palmitoylation by individual mutation of cysteine 561, 562, or 565 or treatment of cells with 2-bromopalmitate shifts GRK6A from the PM to both the cytoplasm and nucleus. Likewise, disruption of the hydrophobic nature of a predicted amphipathic helix by mutation of two leucines to alanines at positions 551 and 552 causes a loss of PM localization. Moreover, acidic amino acids in the C-terminus appear to negatively regulate PM localization; mutational replacement of several acidic residues with neutral or basic residues rescues PM localization of a palmitoylation-defective GRK6A. Last, we characterize the novel nuclear localization, showing that nuclear export of nonpalmitoylated GRK6A is sensitive to leptomycin B and that GRK6A contains a potential nuclear localization signal. Our results suggest that the C-terminus of GRK6A contains a novel electrostatic palmitoyl switch in which acidic residues weaken the membrane-binding strength of the amphipathic helix, thus allowing changes in palmitoylation to regulate PM versus cytoplasmic/nuclear localization.

Sphingosine Kinase Type 2 Activation by ERK-mediated Phosphorylation

Sphingosine 1-phosphate (S1P), a potent lipid mediator, is a ligand for a family of five G protein-coupled receptors (S1P(1-5)) that have been shown to regulate a variety of biological responses important for cancer progression. The cellular level of S1P is low and tightly regulated in a spatio-temporal manner through its synthesis catalyzed by two sphingosine kinases, denoted SphK1 and SphK2. Many stimuli activate and translocate SphK1 to the plasma membrane by mechanisms that are dependent on its phosphorylation. Much less is known about activation of SphK2. Here we demonstrate that epidermal growth factor (EGF) as well as the protein kinase C activator, phorbol ester, induce rapid phosphorylation of hSphK2 which was markedly reduced by inhibition of MEK1/ERK pathway. Down-regulation of ERK1 blocked EGF-induced phosphorylation of SphK2. Recombinant ERK1 phosphorylated hSphK2 in vitro and increased its enzymatic activity. ERK1 also was found to be in a complex with hSphK2 in vivo. Site-directed mutagenesis indicated that hSphK2 is phosphorylated on Ser-351 and Thr-578 by ERK1 and that phosphorylation of these residues is important for EGF-stimulated migration of MDA-MB-453 cells. These studies provide the first clues to the mechanism of agonist-mediated SphK2 activation and enhance understanding of the regulation of SphK2 activity by phosphorylation and its role in movement of human breast cancer cells toward EGF.

CAMP activation of PKA defines an ancient signaling mechanism

cAMP and the cAMP binding domain (CBD) constitute a ubiquitous regulatory switch that translates an extracellular signal into a biological response. The CBD contains alpha- and beta-subdomains with cAMP binding to a phosphate binding cassette (PBC) in the beta-sandwich. The major receptors for cAMP in mammalian cells are the regulatory subunits (R-subunits) of PKA where cAMP and the catalytic subunit compete for the same CBD. The R-subunits inhibit kinase activity, whereas cAMP releases that inhibition. Here, we use NMR to map at residue resolution the cAMP-dependent interaction network of the CBD-A domain of isoform Ialpha of the R-subunit of PKA. Based on H/D, H/H, and N(z) exchange data, we propose a molecular model for the allosteric regulation of PKA by cAMP. According to our model, cAMP binding causes long-range perturbations that propagate well beyond the immediate surroundings of the PBC and involve two key relay sites located at the C terminus of beta(2) (I163) and N terminus of beta(3) (D170). The I163 site functions as one of the key triggers of global unfolding, whereas the D170 locus acts as an electrostatic switch that mediates the communication between the PBC and the B-helix. Removal of cAMP not only disrupts the cap for the B' helix within the PBC, but also breaks the circuitry of cooperative interactions stemming from the PBC, thereby uncoupling the alpha- and beta-subdomains. The proposed model defines a signaling mechanism, conserved in every genome, where allosteric binding of a small ligand disrupts a large protein-protein interface.

Novel Trigger Mechanism High-Power Switch: The Electrostatic Plasma Injection Switch

High-power gas switches like the Pseudospark have been developed for decades, and past research has focused on the trigger mechanism of Pseudospark. This paper presents a new type of switch called the electrostatic plasma injection switch (EPIS), which uses transmission-line reflections of incoming trigger pulse to generate voltage gradients on a vertical multisection trigger structure that extends from a hollow cathode into a symmetrical hollow anode. Low-current preionization glow discharge at the bottom of the cathode region provides seed electrons for fast turn on. The trigger voltage injects plasma into the trigger structure and then accelerates plasma vertically into the gap between anode and cathode. Similar to Pseudospark, a superdense-glow-discharge plasma is responsible for the high current. The trigger electron density is measured by optical spectroscopy to be 3times1015/cm3 inside the hollow cathode and 8times1014/cm3 at the anode-cathode gap. plasma injection speed is 1-4times107 cm/s between 0.1and 0.4-torr pressure and is proportional to pressure and trigger voltage. Delay time decreases when the pressure increases. The EPIS has been operated at 16.6-kV hold-off voltage and 4.96 kA with 95 mtorr of hydrogen. This switch operates in the left-hand branch of the Paschen curve, as do Thyratron and Pseudospark, but it should provide better trigger reliability and higher current capability. Hold-off voltage is limited by local field emission. This device is operational, and waveforms of anode voltage, anode current, trigger voltage, and plasma emissions are recorded. Future applications are discussed

Molecular dynamics of a biophysical model for β 2-adrenergic and G protein-coupled receptor activation

This study analyzes 16 molecular dynamic simulations of a biophysical model for β 2-adrenergic (B2AR) and G protein-coupled receptor (GPCR) activation. In this model, a highly conserved cysteine residue, C106 (C3.25 or CysIII:01), provides a free sulfhydryl or thiol group in an acid–base equilibrium between uncharged (RSH) and charged (RS −) states that functions as an electrostatic molecular switch for receptor activation. The transition of C106 in the B2AR between acid and base states significantly changes the helical/transmembrane (TM) domain interactions and the electrostatic interaction energy differences (ΔΔ E EL). The ΔΔ E EL changes correlate well with the experimentally observed ligand efficacies. The TM interaction energies display patterns compatible with those previously recognized as responsible for GPCR activation. Key differences between the agonist, epinephrine, and the antagonist, pindolol, are seen for the TM3 × 6, TM3 × 4, TM6 × 7 and TM1 × 7 interaction energies. Pindolol also produces a weaker ΔΔ E EL interaction and less TM interaction energy changes, which are important differences between the agonist and antagonist ligands. The D115E mutant with pindolol displays a greater ΔΔ E EL and TM interactions than for the wild-type B2AR with pindolol. This explains the higher activity of pindolol in the D115E mutant. The constitutively active D130A mutant displays TM interaction patterns similar to those for the activating ligands implying a common pattern for receptor activation. These findings support the broad concept of protean agonism and demonstrate the potential for allosteric modulation. They also demonstrate that this two-state model agrees with many previous experimental and theoretical observations of GPCRs.

Identification of a novel gill-specific calpain from rainbow trout (Oncorhynchus mykiss)

Calpains are calcium-dependent neutral proteases responsible for many cellular functions. The two forms of calpain ubiquitously expressed in mammalian tissues are known as mu-calpain and m-calpain. We report here the identification of a novel calpain that is similar to but distinct from the mu- and m-calpains in rainbow trout. The cDNA of the novel gene is 2623 bp in length with a single open reading frame. The predicted protein (676 amino acids) contains the conserved calpain characteristic domains that include: domain I (pro peptide), II (cysteine catalytic site), III (electrostatic switch), and IV (calmodulin-like) with five Ca(2+)-binding EF hands. Northern blot and RT-PCR analyses demonstrated that the novel calpain gene is predominantly expressed in rainbow trout gills. Comparison of the novel protein with the ubiquitously expressed calpains and several mammalian tissue-specific calpains revealed that the novel calpain is an orthologue of the mammalian digestive tract specific calpain (calpain 9).

A simple electrostatic switch important in the activation of type I protein kinase A by cyclic AMP

Cyclic AMP activates protein kinase A by binding to an inhibitory regulatory (R) subunit and releasing inhibition of the catalytic (C) subunit. Even though crystal structures of regulatory and catalytic subunits have been solved, the precise molecular mechanism by which cyclic AMP activates the kinase remains unknown. The dynamic properties of the cAMP binding domain in the absence of cAMP or C-subunit are also unknown. Here we report molecular-dynamics simulations and mutational studies of the RIalpha R-subunit that identify the C-helix as a highly dynamic switch which relays cAMP binding to the helical C-subunit binding regions. Furthermore, we identify an important salt bridge which links cAMP binding directly to the C-helix that is necessary for normal activation. Additional mutations show that a hydrophobic "hinge" region is not as critical for the cross-talk in PKA as it is in the homologous EPAC protein, illustrating how cAMP can control diverse functions using the evolutionarily conserved cAMP-binding domains.