Classical cadherin cell-cell adhesion proteins play key morphogenetic roles during development and are essential for maintaining tissue integrity in multicellular organisms. cadherins bind two distinct conformations, X-dimer strand-swap dimer; cellular rearrangements, these adhesive states exposed to mechanical stress. However, the molecular mechanisms by which resist tensile force pathway they convert between different conformations unclear. Here, we use single molecule measurements with an...

Abstract Self‐propelled lipid‐based artificial cells that can achieve controlled rotation and directed translation present significant potential for biomedical applications, yet their engineering poses considerable challenges. Lipid vesicles synthesized via solution‐based methods naturally adopt isotropic spherical shapes. Active motion of these objects requires symmetry breaking rigidity. In this study, giant are employed as chassis, utilizing enzymes undergo cyclic, non‐reciprocal...

Adhesion between cells is established by the formation of specialized intercellular junctional complexes, such as desmosomes. Desmosomes comprise two members cadherin superfamily cell adhesion proteins, desmocollin (Dsc) and desmoglein (Dsg), but their combinatorial roles in desmosome assembly not understood. To uncouple from other cell-cell we used micro-patterned substrates Dsc2aFc and/or Dsg2Fc collagen IV; show that Dsc2aFc, Dsg2Fc, was necessary sufficient to recruit desmosome-specific...

Core-shell ZnO:MgO nanocrystals have been synthesized by a sequential preparative procedure and capped with carboxymethyl beta-cyclodextrin (CMCD) cavities, thereby rendering the surface of hydrophilic particles water-soluble. The water-soluble CMCD-capped emit strongly in visible region (450-680 nm) on excitation UV radiation are stable over extended periods range pH values. integrity cyclodextrin cavities is preserved capping retains their capability for complexation hydrophobic species...

Abstract Tip-links in the inner ear convey force from sound and trigger mechanotransduction. Here, we present evidence that tip-links (collectively as heterotetrameric complexes of cadherins) function filters during Our force-clamp experiments reveal tip-link show slip-ideal-slip bond dynamics. At low forces, lifetime complex drops monotonically, indicating slip-bond The ideal bond, rare nature, is seen an intermediate regime where survival remains constant over a wide range. large follow...

Oleate-capped ZnO:MgO nanocrystals have been synthesized that are soluble in nonpolar solvents and which emit strongly the visible region (450−600 nm) on excitation by UV radiation. The emission involves recombination of trap states nanocrystalline ZnO core has a higher quantum yield than band gap exciton emission. spectrally resolved dynamics investigated time-resolved spectroscopy. time-evolution photoluminescence spectra show there are, fact, two features whose relative importance...

Cadherin-23 (Cdh23), a long-chain non-classical cadherin, exhibits strong homophilic and heterophilic binding. The physiological relevance of binding with protocadherin-15 at neuroepithelial tip links is well-studied. However, the role Cdh23 homodimers in physiology less understood, despite its widespread expression cell boundaries various human mouse tissues, including kidney, muscle, testes, heart. Here, we performed immunofluorescence studies that revealed present as distinct puncta...

Abstract The euglenatides are a family of hybrid polyketide-nonribosomal peptides produced by the unicellular algae Euglena gracilis . These compounds have antiproliferative activity against fungal pathogens and mammalian cancer cell lines. Analysis E. extracts revealed that produce not only euglenatides, but also corresponding analogs same molecular weights as lacking characteristic triene chromophore. In comparison to these is greatly reduced in cytotoxicity assay, indicating critical...

Single-point mutations are pivotal in molecular zoology, shaping functions and influencing genetic diversity evolution. Here we study three such variants of a mechano-responsive protein, cadherin-23, that uphold the structural integrity but showcase distinct genotypes phenotypes. The exhibit subtle differences transient intra-domain interactions, which turn affect anti-correlated motions among constituent β-strands. In nature, experience declining with aging at different rates. We expose...

Titin, a giant protein (~3-4 MDa), functions as molecular-spring to regulate muscle elasticity. More than 90% of Titin is composed domains that absorb mechanical energy and undergo stochastic unfolding-refolding under tension (~tens pN). These are connected in tandem by interdomain linkers (IDLs), which constitute less 10% the total mass. Despite their small genomic footprint, bioinformatics mapping suggests IDLs have an outsized impact on mechanics, potentially contributing disease...

Polyproteins, individual protein units joined covalently in tandem, have evolved as a promising tool for measuring the dynamic folding of biomacromolecules single-molecule force spectroscopy. However, synthetic routes to prepare polyproteins been bottleneck, and urge development vitro methods knit into polyprotein. Employing two enzymes orthogonal functionalities periodically sequence, we synthesized monodispersed on solid surface. We used Sortase A (SrtA), enzyme known sequence specific...

We have developed a method for Enzymatic Sortase-assisted Covalent Orientation-specific Restraint Tethering (ESCORT) recombinant proteins onto surfaces directly from cell-lysate. With an improved surface passivation method, we obviate the cumbersome purification steps even single molecule studies that demand high purity in sample. demonstrated high-specificity of high-passivity and uncompromised functional integrity anchored using fluorescence force-mapping. anticipate this will...

Fluorescent probes are essential for imaging of cancer cells and tracking organelles inside cells. We have synthesized three molecular rotors AIN, AINP F-AINP based on 1-aminoindole (AI) as an electron donor naphthalimide acceptor. All compounds showed charge transfer (CT) character, aggregation induced emission (AIE) responsiveness towards temperature variation solvent viscosity. was most sensitive viscosity among all molecules with a sensitivity ∼0.37. negative coefficients in chloroform...

Abstract Cis and trans-interactions among cadherins secure multicellularity. While the molecular structure of is well understood, work to identify cues that spread cis-interactions two-dimensionally still ongoing. Here, we report transient, weak, yet multivalent, spatially distributed hydrophobic interactions are involved in liquid-liquid phase separations biomolecules solution, alone can drive lateral-clustering cadherin-23 on a membrane. No specific cis-dimer required for lateral...

Evolutionarily elderly proteins commonly feature greater catalytic promiscuity. Cytochrome c is among the first set of in evolution to have known prospects electron transport and peroxidative properties. Here, we report that cyt also a proficient proton-transfer catalyst enhances Kemp elimination (KE; model reaction show proton transfer property) by ∼750-fold on self-organized systems like micelles vesicles. The mimic mitochondrial environment vitro for c. Using an array biophysical...

Tip-link as force-sensor in hearing conveys the mechanical force originating from sound to ion-channels while maintaining integrity of entire sensory assembly inner ear. This delicate balance between structure and function tip-links is regulated by Ca2+-ions present endolymph. Mutations at Ca2+-binding sites often lead congenital deafness, sometimes syndromic defects impairing vision along with hearing. Although such mutations are already identified, it still not clear how mutants alter...

Cadherin‐23, a giant atypical cadherin, form homophilic interactions at the cell–cell junction of epithelial cells and heterophilic with protocadherin‐15 tip links neuroepithelial cells. While molecular structure heterodimer is solved, homodimer yet to be resolved. The homodimers play an essential role in adhesion as downregulation cadherin‐23 cancers loosen intercellular resulting faster migration cancer significant drop patient survival. In vitro studies have measured stronger aggregation...

Resonance energy transfer (RET) from the visible emission of core−shell ZnO:MgO nanocrystals to Nile Red chromophores, following band gap excitation in UV, has been investigated for four different nanocrystal sizes. With use steady state and time-resolved fluorescence spectroscopic measurements wavelength dependent RET efficiencies have determined. The process occurs emissions involving trap recombination. There are two such processes with same particle size. This is shown be a consequence...

Age-related hearing loss (ARHL) is a common condition in humans marking the gradual decrease with age. Perturbations tip-link protein cadherin-23 that absorbs mechanical tension from sound and maintains integrity of associated ARHL. Here, search molecular origins for ARHL, we dissect conformational behavior along mutant S47P progresses drastically. Using an array experimental computational approaches, highlight lower thermodynamic stability, significant weakening hydrogen-bond network...

Proteins as force-sensors respond to mechanical cues and regulate signaling in physiology. commonly connect the source response points of two conformations, independent proteins end-to-end geometry protein complexes handshake geometry. The force-responsive property is studied extensively using single-molecule force spectroscopy (SMFS). physiological significance complex conformations force-sensing often disregarded mere surge protectors. However, with potential force-steering, possess a...

Charged polysaccharides play an essential role in biology and also serve as a promising class of biomaterials. We demonstrate, at the single molecule level, simple method to cross-link anionic using polyions electrostatic staples; positive charges on polyion bridge opposite polysaccharide trap its conformation. Cross-linking is detected by measuring step-like conformational transitions when are stretched Atomic Force Microscope (AFM). The probability cross-linking can be tuned either...