Helical Interface Research Articles

Disrupting the hydrophobic lock in MscL in molecular dynamics simulations

MscL, a large-conductance mechanosensitive (MS) ion channel, functions as a fast osmolyte release valve to reduce hydrostatic pressure within the cytoplasmic membrane upon osmotic shock. These membrane proteins play a crucial role in fundamental biological processes, including but not limited to blood and osmotic pressure regulation, touch and pain-sensing, and cardiovascular control. In this work, we study the effects of disrupting the ‘hydrophobic lock’ in M. tuberculosis wild-type MscL through mutations (V21T, V21A, V21T, and A20N) at the interface of transmembrane helix 2 that lines the pore.

Design and Synthesis of Crosslinked Helix Dimers as Protein Tertiary Structure Mimics.

Crosslinked helix dimers (CHDs) are synthetic tertiary helical structure motifs designed to modulate interactions of proteins with binding partners. Helix dimers serve as mimics of coiled coils, which are known to be implicated in a multitude of protein complexes. Coiled coils are typically stable in long peptides (>21-28 residues), because sufficient intra- and interstrand contacts are not available in short peptides to coax strand assembly. To engineer conformationally stable CHDs in short sequences, we introduced a covalent linkage in place of an interhelical salt bridge and sculpted the helical interface with optimal hydrophobic packing. CHDs have shown efficacy for the disruption of targeted protein-protein interactions in biochemical, cellular, and animal models. This article describes our optimized approach to design and synthesize parallel and antiparallel helical tertiary structure mimics. Synthesis of CHDs involves conjugation of individual peptide segments, purification of the mono-conjugated strand, and alkylation of the two independent strands to yield crosslinked dimers. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Protocol for bis-triazole CHDs Basic Protocol 2: Protocol for dibenzyl ether CHDs.

Conformational Clamping by a Membrane Ligand Activates the EphA2 Receptor

The EphA2 receptor is a promising drug target for cancer treatment, since EphA2 activation can inhibit metastasis and tumor progression. It has been recently described that the TYPE7 peptide activates EphA2 using a novel mechanism that involves binding to the single transmembrane domain of the receptor. TYPE7 is a conditional transmembrane (TM) ligand, which only inserts into membranes at neutral pH in the presence of the TM region of EphA2. However, how membrane interactions can activate EphA2 is not known. We systematically altered the sequence of TYPE7 to identify the binding motif used to activate EphA2. With the resulting six peptides, we performed biophysical and cell migration assays that identified a new potent peptide variant. We also performed a mutational screen that determined the helical interface that mediates dimerization of the TM domain of EphA2 in cells. These results, together with molecular dynamic simulations, allowed to elucidate the molecular mechanism that TYPE7 uses to activate EphA2, where the membrane peptide acts as a molecular clamp that wraps around the TM dimer of the receptor. We propose that this binding mode stabilizes the active conformation of EphA2. Our data, additionally, provide clues into the properties that TM ligands need to have in order to achieve activation of membrane receptors.

Abstract 2270: Membrane organization of KRas4B with regulatory domain of Raf-1

Abstract A major pathway in RAS-driven cell proliferation is the MAPK (Raf/MEK/ERK) pathway. In cancer, membrane-anchored, proximally located, oncogenic Ras isoforms promote Raf dimerization and fully activate MAPK signaling. Among Ras isoforms, KRas4B is frequently mutated in cancer. In the MAPK pathway, active KRas4B dimer or nanocluster can lead to dimerization of Raf kinase domain enhancing the affinity of the KRas4B-Raf interaction. Recently, we modeled the binary KRas4B-Raf-1 complex and its quaternary assembly with the regulatory domain of Raf-1 containing the Ras binding domain (RBD) and cysteine-rich domain (CRD), and suggested that Raf-1 CRD bolsters the high-affinity interaction of Raf-1 with KRas4B by reducing the KRas4B-RBD fluctuations. For the quaternary assembly, recent in silico studies suggested that KRas4B dimer is aligned through the α3 and α4 helical interface, not the α4 and α5 helical interface due to hindrance to the membrane contact of Raf-1 CRD. The Raf-1 regulatory domain contains the N-terminal region (residues 1-55), RBD, and CRD. However, previous modeling efforts were conducted for the KRas4B-Raf-1 complex in the absence of the N-terminal region. Here, computational studies were performed for the KRas4B-Raf-1 complex with full sequence of Raf-l regulatory domain interacting with monomeric and dimeric KRas4B-GTP at the membrane. Increasing experimental evidences suggested that the N-terminal region of Raf plays a significant role in the Ras interaction and the membrane anchorage of Raf. The membrane interaction of isolated N-terminal segment was investigated as the first step toward the complex model construction. Since oncogenic KRas4B mutants form dimers/nanoclusters at the membrane microdomains that provide the signaling platform for Raf, KRas4B in different mutation states interacting with the membrane microdomains with different lipid composition was also studied. The presence of the N-terminal segment of Raf-1 regulatory domain at the membrane can enhance the stability of KRas4B-Raf-1 and thereby relieving Raf's autoinhibition toward a kinase domain-accessible state, providing a complete mechanistic picture of the KRas4B-Raf-1 interaction. Our recent work uncovers the mechanism of Raf-1 activation by KRas4B at atomic resolution and highlight how this may help in elucidating vital mechanistic questions in Ras biology. Funded by Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E. Citation Format: Hyunbum Jang, Mingzhen Zhang, Ruth Nussinov. Membrane organization of KRas4B with regulatory domain of Raf-1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2270.

Topology-Switching Membrane Peptides for Determination of the Active Transmembrane Dimer Interface of the Epha2 Receptor

The EphA2 receptor tyrosine kinase is an interesting target for cancer therapeutics, as its rogue activation promotes tumor growth and metastasis. EphA2 activation is sensitive to dimerization induced by its single transmembrane (TM) domain. We thus previously designed the pH-sensitive TYPE7 peptide, which selectively activates EphA2 by binding its TM domain (Alves et al. eLife, 2018). TYPE7 comprises the TM sequence of EphA2, but with Glutamate residues added onto one helical face. To study the mechanism of TYPE7-induced EphA2 activation, we systematically rotated the Glu-containing helical interface. We performed biophysical and cell biology techniques on the six resulting peptides and molecular dynamics (MD) simulations on two, to study their effect on TM binding and activation of EphA2. First, we studied the interaction of the peptides with the membrane region of EphA2 reconstituted in lipid vesicles. We observed that the peptides are helical in the membrane, and most of them interact with EphA2. However, several peptides failed to activate EphA2 in cells, as assessed by EphA2-mediated cell migration. Next, we performed MD simulations to understand why similar peptides affect EphA2 activation differently. We observed that an activating peptide stabilizes the EphA2 TM dimer in a glycine zipper conformation. In contrast, a non-activating peptide stabilizes a complex in which the EphA2 helices are separated in a non-native, not-activation-competent conformation. The MD results suggest a mechanism for TYPE7-induced EphA2 activation, where peptide binding stabilizes the more active TM conformation. This provides support for the ligand-induced rotation hypothesis for RTK activation, where different helical interfaces correspond to active and inactive states. Additionally, these studies provide a basis for the specificity of TYPE7, since changing the available TM interface results in an EphA2 TM conformation that is less activation-competent.

Dirac points and the transition towards Weyl points in three-dimensional sonic crystals

A four-fold-degenerate three-dimensional (3D) Dirac point, represents a degenerate pair of Weyl points carrying opposite chiralities. Moreover, 3D Dirac crystals have shown many exotic features different from those of Weyl crystals. How these features evolve from 3D Dirac to Weyl crystals is important in research on 3D topological matter. Here, we realized a pair of 3D acoustic Dirac points from band inversion in a hexagonal sonic crystal and observed the surface states and helical interface states connecting the Dirac points. Furthermore, each Dirac point can transition into a pair of Weyl points with the introduction of chiral hopping. The exotic features of the surface states and interface states are inherited by the resulting Weyl crystal. Our work may serve as an ideal platform for exploring exotic physical phenomena in 3D topological semimetals.

Phosphorylation Promotes Aβ25-35 Peptide Aggregation within the DMPC Bilayer.

The consequences of phosphorylation of the Aβ25-35 peptide at the position Ser26 on its aggregation have not been examined. To investigate them, we performed all-atom replica exchange simulations probing the binding of phosphorylated Aβ25-35 (pAβ25-35) peptides to the dimyristoyl phosphatidylcholine (DMPC) bilayer and their subsequent aggregation. As a control, we used our previous study of unmodified peptides. We found that phosphorylation moderately reduces the helical propensity in pAβ25-35 and its binding affinity to the DMPC bilayer. Phosphorylation preserves the bimodal binding observed for unmodified Aβ25-35, which features a preferred inserted state and a less probable surface bound state. Phosphorylation also retains the inserted dimer with a head-to-tail helical aggregation interface as the most thermodynamically stable state. Importantly, this post-translation modification strengthens interpeptide interactions by adding a new aggregation "hot spot" created by cross-bridging phosphorylated Ser26 with water, cationic ions, or Lys28. The cross-bridging constitutes the molecular mechanism behind most structural phosphorylation effects. In addition, phosphorylation eliminates pAβ25-35 monomers and diversifies the pool of aggregated species. As a result, it changes the binding and aggregation mechanism by multiplying pathways leading to stable inserted dimers. These findings offer a plausible molecular rationale for experimental observations, including enhanced production of low molecular weight oligomers and cytotoxicity of phosphorylated Aβ peptides.

A dynamic anchor domain in slc13 transporters controls metabolite transport

Metabolite transport across cellular membranes is required for bioenergetic processes and metabolic signaling. The solute carrier family 13 (slc13) transporters mediate transport of the metabolites succinate and citrate and hence are of paramount physiological importance. Nevertheless, the mechanisms of slc13 transport and regulation are poorly understood. Here, a dynamic structural slc13 model suggested that an interfacial helix, H4c, which is common to all slc13s, stabilizes the stationary scaffold domain by anchoring it to the membrane, thereby facilitating movement of the SLC13 catalytic domain. Moreover, we found that intracellular determinants interact with the H4c anchor domain to modulate transport. This dual function is achieved by basic residues that alternately face either the membrane phospholipids or the intracellular milieu. This mechanism was supported by several experimental findings obtained using biochemical methods, electrophysiological measurements in Xenopus oocytes, and fluorescent microscopy of mammalian cells. First, a positively charged and highly conserved H4c residue, Arg108, was indispensable and crucial for metabolite transport. Furthermore, neutralization of other H4c basic residues inhibited slc13 transport function, thus mimicking the inhibitory effect of the slc13 inhibitor, slc26a6. Our findings suggest that the positive charge distribution across H4c domain controls slc13 transporter function and is utilized by slc13-interacting proteins in the regulation of metabolite transport.

A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission.

The ESCRT complexes drive membrane scission in HIV-1 release, autophagosome closure, MVB biogenesis, cytokinesis, and other cell processes. ESCRT-I is the most upstream complex and bridges the system to HIV-1 Gag in virus release. The crystal structure of the headpiece of human ESCRT-I comprising TSG101–VPS28–VPS37B–MVB12A was determined, revealing an ESCRT-I helical assembly with a 12 molecule repeat. Electron microscopy confirmed that ESCRT-I subcomplexes form helical filaments in solution. Mutation of VPS28 helical interface residues blocks filament formation in vitro and autophagosome closure and HIV-1 release in human cells. Coarse grained simulations of ESCRT assembly at HIV-1 budding sites suggest that formation of a 12-membered ring of ESCRT-I molecules is a geometry-dependent checkpoint during late stages of Gag assembly and HIV-1 budding, and templates ESCRT-III assembly for membrane scission. These data show that ESCRT-I is not merely a bridging adaptor, but has an essential scaffolding and mechanical role in its own right.

Quantized Field-Effect Tunneling between Topological Edge or Interface States.

We study the tunneling through a two-dimensional topological insulator with topologically protected edge states. It is shown that the tunneling probability can be quantized in a broad parameter range, 0 or 1, tuned by an applied transverse electric field. Based on this field-effect tunneling, we propose two types of topological transistors based on helical edge or interface states of quantum spin Hall insulators separately. The quantized tunneling conductance is obtained and shown to be robust against nonmagnetic disorders. Usually, the topological transition is necessary in the operation of topological transistors. These findings provide a new strategy for the design of topological transistors without topological transitions.

Functional Coiled-Coil-like Assembly by Knob-into-Hole Packing of Single Heptad Repeat.

Coiled-coil peptides represent the principal building blocks for structure-based design of bionanomaterials. The sequence-structure relationship and precise nanoscale ordering of the coiled-coil helices originate from the knob-into-hole (KIH) packing of side chains. The helical interface stabilized by the KIH interaction is known to have chain lengths ranging from 30 to 1000 residues. Yet the shortest peptide required for oligomerization through KIH assembly is still unknown. Here, we report that through atomic resolution a minimal seven-residue amphipathic helix forms a different type of KIH motif, termed "supramolecular KIH packing", which confers an exceptional stability to the helical dimers. Significantly, at a low pH, the peptide self-assembles into nanofibers with coiled-coil architecture resembling the natural fibrous proteins. Furthermore, hierarchical ordering of the nanofibers affords lyotropic liquid crystals composed of a shortest natural helical sequence. Thus, this study expands the sequence space for a coiled-coil folding manifold and provides another paradigm for designer nanomaterials from minimal helical sequences.

Abstract 2763: Raf-1 cysteine-rich domain (CRD) promotes active KRas4B membrane orientation facilitating dimerization through the allosteric lobe interface

Abstract Ras proteins are classical members of small GTPases, controlling signal transduction pathways and promoting cell proliferation. Ras consists of highly homologous catalytic domains and flexible C-terminal hypervariable regions (HVRs) that differ significantly across Ras isoforms. Ras activation is regulated by guanine nucleotide exchange factors that catalyze the exchange of GDP by GTP, and activation is terminated by GTPase-activating proteins that induce the GTP hydrolysis. Ras has multiple partners, signals through several key pathways and fulfills critical functions in the cell life. Mutations in Ras are common in a variety of cancers; yet it is still undruggable. KRas4B is frequently mutated in cancer. Elucidation of Ras conformational ensembles at the signaling platforms in the plasma membrane including the ligand-bound conformations, membrane orientations, the activated (or inactivated) allosteric modulated states, post-translationally modified states, mutational states, and transition states are essential for deciphering Ras functions from its conformational landscapes. In the MAPK pathway, KRas4B preferentially recruits Raf-1 and activates it. Raf kinases contain Ras binding domain (RBD) and cysteine-rich domain (CRD) at conserved region 1 (CR1), and kinase domain at CR3. The high-affinity interaction of Raf RBD with Ras was solved in the absence of CRD. It is known that Raf CRD play a key role in the membrane anchoring mechanism. Recently, pivotal roles of CRD in the membrane interactions of KRas4B-Raf-1 RBD-CRD complex were reported. Here, we employ all-atom molecular dynamics (MD) simulations to investigate dimeric KRas4B-Raf-1 complex at the anionic lipid bilayer composed of DOPC and DOPS (4:1). Active KRas4B dimer modulates Raf-1 activation, promoting dimerization of Raf-1’s kinase domain. In the dimeric complex of KRas4B-Raf-1, Raf-1 CRD stably binds anionic lipid bilayers inserting its positively-charged loop into the amphipathic interface. The key basic residues at the loop are responsible for the membrane association, suggesting that CRD is an intrinsic membrane binding domain of Raf kinase. Our simulations suggest that Raf-1 CRD not only offers an additional membrane anchor for the KRas4B-Raf-1 complex, but also reduces the fluctuations of Ras-RBD, enhancing the high affinity interaction between Ras and Raf. Raf-1 CRD supports the active-state Ras orientation, promoting Ras dimerization through the allosteric lobe helical interface at the membrane. The enhanced stability of the complex at the membrane rendered by CRD promotes Raf dimerization in the MAPK signaling, which is the key Ras proliferative pathway. Here we suggest these significant roles of CRD at the membrane in the Raf activation. Funded by Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E. Citation Format: Hyunbum Jang, Ruth Nussinov. Raf-1 cysteine-rich domain (CRD) promotes active KRas4B membrane orientation facilitating dimerization through the allosteric lobe interface [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2763.

Sterical Recognition at Helix-Helix Interface of Leu-Aib-Based Polypeptides with and without a GxxxG-Motif.

An amphiphilic polypeptide, poly(sarcosine)- b-(l-Leu-Aib)8 (SL16), was reported to self-assemble into vesicles. A GxxxG motif, which is known to induce helix dimerization, is incorporated into the hydrophobic helical block of SL16 to synthesize poly(sarcosine)- b-(l-Leu-Aib)2-(Gly-Aib-l-Leu-Aib-Gly-Aib)-(l-Leu-Aib)3 (SG16). SG16 shows helix association in ethanol at a high concentration and low temperatures, which is not observed with SL16. SG16 self-assembles into vesicles, but are found to be more susceptible to rupture by the addition of Triton X-100 than SL16 vesicles. A mixture of SL16 and SG16 self-assembles into small sheets and micelles likely because of mismatch of the modes of helix association arising from sterical accommodation of iso-butyl groups at the helix-helix interface.

Local magnetization of GeTe/Sb2Te3 superlattice films using a scanning probe microscope

Local magnetization of chalcogenide superlattices (SL) of [(GeTe)2 (Sb2Te3)]n (n=4 and 8) was performed using a magnetic force microscopy (MFM) at room temperature. We show that stripe patterns appeared in MFM phase images after magnetizing of the SL by holding the MFM probe at a short distance to the SL surface at room temperature. The probe-induced stripe pattern remained after storage for several days, and which differs from electric poling. We attributed the SL magnetization to the imbalance in the amount of spin-up and spin-down carriers in helical interface bands under the stray magnetic field.

Transmembrane TM3b of Mechanosensitive Channel MscS Interacts With Cytoplasmic Domain Cyto-Helix.

The mechanosensitive channel MscS functions as an osmolyte emergency release-valve in the event of a sudden decrease in external environmental osmolarity. MscS has served as a paradigm for studying how channel proteins detect and respond to mechanical stimuli. However, the inter-domain interactions and structural rearrangements that occur in the MscS gating process remain largely unknown. Here, we determined the interactions between the transmembrane domain and cytoplasmic domain of MscS. Using in vivo cellular viability, single-channel electrophysiological recording, and cysteine disulfide trapping, we demonstrated that N117 of the TM3b helix and N167 of the Cyto-helix are critical residues that function at the TM3b-Cyto helix interface. In vivo downshock assays showed that double cysteine substitution at N117 and N167 failed to rescue the osmotic-lysis phenotype of cells in acute osmotic downshock. Single-channel recordings demonstrated that cysteine cross-linking of N117C and N167C led to a non-conductive channel. Consistently, coordination of the histidines of N117H and N167H caused a decrease in channel gating. Moreover, cross-linked N117 and N167 altered the gating of the severe gain-of-function mutant L109S. Our results demonstrate that N117–N167 interactions stabilize the inactivation state by an association of TM3b segments with β-domains of the cytoplasmic region, providing further insights into the gating mechanism of the MscS channel.

Proteomic analysis of monolayer-integrated proteins on lipid droplets identifies amphipathic interfacial α-helical membrane anchors

Despite not spanning phospholipid bilayers, monotopic integral proteins (MIPs) play critical roles in organizing biochemical reactions on membrane surfaces. Defining the structural basis by which these proteins are anchored to membranes has been hampered by the paucity of unambiguously identified MIPs and a lack of computational tools that accurately distinguish monolayer-integrating motifs from bilayer-spanning transmembrane domains (TMDs). We used quantitative proteomics and statistical modeling to identify 87 high-confidence candidate MIPs in lipid droplets, including 21 proteins with predicted TMDs that cannot be accommodated in these monolayer-enveloped organelles. Systematic cysteine-scanning mutagenesis showed the predicted TMD of one candidate MIP, DHRS3, to be a partially buried amphipathic α-helix in both lipid droplet monolayers and the cytoplasmic leaflet of endoplasmic reticulum membrane bilayers. Coarse-grained molecular dynamics simulations support these observations, suggesting that this helix is most stable at the solvent-membrane interface. The simulations also predicted similar interfacial amphipathic helices when applied to seven additional MIPs from our dataset. Our findings suggest that interfacial helices may be a common motif by which MIPs are integrated into membranes, and provide high-throughput methods to identify and study MIPs.

Protein and Chemical Determinants of BL-1249 Action and Selectivity for K2P Channels.

K2P potassium channels generate leak currents that stabilize the resting membrane potential of excitable cells. Various K2P channels are implicated in pain, ischemia, depression, migraine, and anesthetic responses, making this family an attractive target for small molecule modulator development efforts. BL-1249, a compound from the fenamate class of nonsteroidal anti-inflammatory drugs is known to activate K2P2.1(TREK-1), the founding member of the thermo- and mechanosensitive TREK subfamily; however, its mechanism of action and effects on other K2P channels are not well-defined. Here, we demonstrate that BL-1249 extracellular application activates all TREK subfamily members but has no effect on other K2P subfamilies. Patch clamp experiments demonstrate that, similar to the diverse range of other chemical and physical TREK subfamily gating cues, BL-1249 stimulates the selectivity filter “C-type” gate that controls K2P function. BL-1249 displays selectivity among the TREK subfamily, activating K2P2.1(TREK-1) and K2P10.1(TREK-2) ∼10-fold more potently than K2P4.1(TRAAK). Investigation of mutants and K2P2.1(TREK-1)/K2P4.1(TRAAK) chimeras highlight the key roles of the C-terminal tail in BL-1249 action and identify the M2/M3 transmembrane helix interface as a key site of BL-1249 selectivity. Synthesis and characterization of a set of BL-1249 analogs demonstrates that both the tetrazole and opposing tetralin moieties are critical for function, whereas the conformational mobility between the two ring systems impacts selectivity. Together, our findings underscore the landscape of modes by which small molecules can affect K2P channels and provide crucial information for the development of better and more selective K2P modulators of the TREK subfamily.

Development of de Novo Copper Nitrite Reductases: Where We Are and Where We Need To Go.

The development of redox-active metalloprotein catalysts is a challenging objective of de novo protein design. Within this Perspective we detail our efforts to create a redox-active Cu nitrite reductase (NiR) by incorporating Cu into the hydrophobic interior of well-defined three-stranded coiled coils (3SCCs). The scaffold contains three histidine residues that provide a layer of three nitrogen donors that mimic the type 2 catalytic site of NiR. We have found that this strategy successfully produces an active and stable CuNiR model that functions for over 1000 turnovers. Spectroscopic evidence indicates that the Cu(I) site has a lower coordination number in comparison to the enzyme, whereas the Cu(II) geometry may more faithfully reproduce the NiR type 2 center. Mutations at the helical interface successfully produce a hydrogen bond between an interfacial Glu residue and the Culigating His residue, which allows for the tuning of the redox potential over a 100 mV range. We successfully created constructs with as much as a 120-fold improvement from the original design by modifying the steric bulk above or below the Cu binding site. These systems are now the most active water-soluble and stable artificial NiR catalysts yet produced. Several avenues for improving the catalytic efficiency of later designs are detailed within this Perspective, including adjustment of their resting oxidation state, the use of asymmetric scaffolds to allow for single amino acid mutation within the second coordination sphere, and the design of hydrogen-bonding networks to tune residue orientation and electronics. Through these studies the TRI-H system has given insight into the difficulties that arise in creating a de novo redox active enzyme. Work to improve upon this model will provide strategies by which redox-active de novo enzymes may be tuned and detail how native enzymes accomplish catalytic efficiencies through proton gated redox catalysis.

Three-Dimensional-Printable Thermoactive Helical Interface With Decentralized Morphological Stiffness Control for Continuum Manipulators

We present a three-dimensional (3-D)-printable thermoactive scale jamming interface as a new way to control a continuum manipulator dexterity by taking inspiration from the helical arrangement of fish scales. A highly articulated helical interface is 3-D-printed with thermoactive functionally graded joints using a conventional 3-D printing device that utilizes UV curable acrylic plastic and hydroxylated wax as the primary and supporting material. The joint compliance is controlled by regulating wax temperature in phase transition. Empirical feed-forward control relations are identified through comprehensive study of the wax melting profile and actuation scenarios for different shaft designs to achieve desirable repeatability and response time. A decentralized control approach is employed by relating the mathematical terms of the Cosserat beam method to their morphological counterparts in which the manipulator local anisotropic stiffness is controlled based on the local stress and strain information. As a result, a minimalistic central controller is designed in which the joints’ thermomechanical states are observed using a morphological observer, an external fully monitored replica of the observed system with the same inputs. Preliminary results for passive shape adaptation, geometrical disturbance rejection, and task space anisotropic stiffness control are reported by integrating the interface on a continuum manipulator.

Long-range effect of a Zeeman field on the electric current through the helical metal-superconductor interface in an Andreev interferometer

It is shown that the spin-orbit and Zeeman interactions result in phase shifts of Andreev-reflected holes in disordered topological insulator, or normal Rashba spin-orbit-coupled wires, which are in a contact with an s-wave superconductor. Due to interference of the holes reflected through different paths in Andreev interferometer the electric current through the contact varies depending on the strength and direction of the Zeeman field. It also depends on mutual orientations of Zeeman fields in different shoulders of the interferometer. Such a nonlocal effect is a result of the long-range coherency caused by the superconducting proximity effect. This current has been calculated within the semiclassical theory for Green functions of a dirty system.