Biology subjects

Kotov, N. A.

Publications and source records attributed to Kotov, N. A..

8 recordsLinked to original sources

bioRxiv2026

MICAL-Inspired Chiral Vanadate Nanoclusters Decelerate Actin Dynamics in Live Cells

Actin turnover is a fundamental cellular process essential for cell dynamics, whose control is critical for both medicine and biotechnology. However, conventional small molecules modifying actin turnover scramble the structure of actin filaments and display high cellular toxicity. MICAL enzymes oxidizing methionine (Met) residues in actin can potentially address this challenge, but their large size and multiple required cofactors make MICALs manufacturing and utilization difficult. Here we show that redox-active chiral decavanadate nanoclusters with tartaric acid are capable of site-selective actin modulation, mimicking MICALs, while requiring no cofactors, displaying high biocompatibility and being membrane permeable. Decavanadate nanoclusters serve as atomically precise "nano-enzymes" oxidizing three Met residues in globular actin, including Met-176; the latter inhibits the opening of the backdoor segment and prevents depolymerization of actin filaments. The structure of actin filaments formed after nanocluster treatment revealed no structural disturbances as confirmed by cryo-electron microscopy. The biocompatibility and bioactivity of chiral decavanadate nanoclusters was demonstrated by modulation of actin in living NG108-15 cells. Taking advantage of atomically precise structure of the nanoclusters, we show that their docking into actin can be predicted computationally, indicating the possibility of programmable actin modulation using the tools of nanochemistry.

biochemistry↗

bioRxiv2026

Enantiomer-Dependent Biological Activity of Cysteine-Coated Ceria Nanoparticles in Colorectal Cancer Cells

Colorectal cancer (CRC) remains a major cause of cancer death, and advanced disease is still limited by resistance and systemic toxicity. We studied intrinsically active, biomimetic cerium oxide nanoparticles (CeNPs) functionalized with D- or L-cysteine (D-Cys@CeNPs and L-Cys@CeNPs) in three CRC cell lines (COLO-201, DLD-1, and LoVo) and healthy colon fibroblasts (CCD-18Co). We propose these materials act as enantioselective functional keys: cysteine stereochemistry shapes recognition at the nano-bio interface, while productive interactions allow the Ce3-rich surface to drive localized redox exchange. We measured viability, ROS as a downstream phenotypic readout, Annexin V/PI-defined cell fate, and expression of the NF-{kappa}B regulatory genes TNFAIP3 (A20), IKBKG (NEMO), and NFKBIA (I{kappa}B). Across the CRC panel, D-Cys@CeNPs caused earlier and stronger loss of viability, with the clearest effect in COLO-201, and shifted cells toward late apoptosis and necrosis. In contrast, L-Cys@CeNPs produced slower and more heterogeneous fate changes. Gene expression showed enantiomer-dependent differences in NF-{kappa}B feedback, consistent with differential pathway engagement. CCD-18Co fibroblasts were comparatively resistant to both enantiomers. Together, these findings link chiral CeNP surface design to redox-linked pathway regulation and support a materials-based route to selective anticancer activity. INTRODUCTION

bioengineering↗

bioRxiv2025

Fourier Helicity Spectra as Quantifiers of Multiscale Chirality

Quantifying the chirality of three-dimensional (3D) objects is crucial for understanding interactions of nanoscale structures, biological molecules, and hierarchical materials. Although chirality is simultaneously present at multiple scales for each case, existing chirality measures rely only on singular scale-specific quantifiers, and some of them yield incorrect chirality assignments for biomolecules. Here we introduce the Fourier Helicity Spectra, a mathematical framework to decompose geometry of chemical and biological structures encompassing the scale dependence of mirror asymmetry. Fourier decomposition of 3D objects into helical harmonics enables one to compute a handedness-resolved characteristics of complex shapes, while reducing computational cost. We show its applicability for a diverse range of chemical systems, from biomacromolecular electron densities to tomographic reconstructions of inorganic nanostructures. Furthermore, inverse transform of isolated spectral components into real space enables visualization of helicity-matched interfaces, identifying how chirality governs biomolecular interactions. We anticipate that this methodology can be generalized with alternative basis sets to encompass a broad range of chiral symmetries governing biological signaling, polarization optics, drug design, and advanced synthesis.

bioinformatics↗

bioRxiv2025

Complexes between Netrin G Ligands and Chiral Nanoparticles Promote Axons Regeneration under Near-Infrared Illumination

Chiral nanoparticles combine functionalities of inorganic materials and large biomacromolecules enabling stimulation of neurons. However, multiple challenges remain in their use for central nervous system including identifying suitable cell signaling pathways and traversing the blood-brain barrier. In this study, we show that glutathione-coated Ni(OH)2 nanoparticles form nanoscale complexes with netrin-G1 ligands (NGL-1), critical for neuronal regeneration. NGL-1 features a semispherical pocket with a 2.5 nm radius of curvature, fitting well with nanoparticles sized 3 {+/-} 1.2 nm. D-NPs with D-glutathione surface ligands activate D-glutathione receptors on epithelial cells, facilitating their transport into the brain. When illuminated with 980 nm light, the nanoparticle-protein complex stimulates axon regeneration through localized IGF-1 production. This approach successfully regenerated (a) hippocampal neurons in Alzheimers disease mice and (b) dorsal root ganglion neurons in spinal cord-injured mice. The nanoparticles were thoroughly tested for safety and excreted intact. The local, rather than systemic, IGF-1 upregulation minimizes its side effects.

neuroscience↗

bioRxiv2021

Automatic structural analysis of bioinspired percolating network materials using graph theory

Mimicking numerous biological membranes and nanofiber-based tissues, there are multiple materials that are structured as percolating nanoscale networks (PPNs). They reveal unique combination of properties and the family of PNN-based composites and nanoporous materials is rapidly expanding. Their technological significance and the necessity of their structural design require a unifying approach for their structural description. However, their complex aperiodic architectures are difficult to describe using traditional methods that are tailored for crystals. A related problem is the lack of computational tools that enable one to capture and enumerate the patterns of stochastically branching fibrils that are typical for these composites. Here, we describe a conceptual methodology and a computational package, StructuralGT, to automatically produce a graph theoretical (GT) description of PNNs from various micrographs. Using nanoscale networks formed by aramid nanofibers (ANFs) as examples, we demonstrate structural analysis of PNNs with 13 GT parameters. Unlike qualitative assessments of physical features employed previously, StructuralGT allows quantitative description of the complex structural attributes of PNNs enumerating the networks morphology, connectivity, and transfer patterns. Accurate conversion and analysis of micrographs is possible for various levels of noise, contrast, focus, and magnification while a dedicated graphical user interface provides accessibility and clarity. The GT parameters are expected to be correlated to material properties of PNNs (e.g. ion transport, conductivity, stiffness) and utilized by machine learning tools for effectual materials design. Table of Content O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/438877v1_ufig1.gif" ALT="Figure 1"> View larger version (144K): org.highwire.dtl.DTLVardef@1c929f0org.highwire.dtl.DTLVardef@1e07168org.highwire.dtl.DTLVardef@357e7aorg.highwire.dtl.DTLVardef@28d21_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

Graph Theoretical Design of Biomimetic Aramid Nanofiber Nanocomposites as Insulation Coatings for Implantable Bioelectronics

An insulation material combining crack and delamination resistance, flexibility, strong adhesion, and biocompatibility is vital for implantable bioelectronic devices of all types. Creating a material with the combination of all these properties is a particularly distinct challenge for implantable electrodes. Here we describe a nanocomposite material addressing these technological challenges based on aramid nanofibers (ANFs) whose unique mechanical properties are complemented by the epoxy resins with strong adhesion to various surfaces. The nanoscale structure of the ANF/epoxy nanocomposite coating replicates the nanofibrous organization of human cartilage, which is known for its exceptional toughness and longevity. The structural analogy between percolating networks of cartilage and ANF was demonstrated using Graph Theory (GT) analysis. The match of multiple GT indexes indicated the near identical organization pattern of cartilage and ANF/epoxy nanocomposite. When compared with the standard insulating material for bioelectronics, Parylene C, the ANF/epoxy nanocomposite demonstrates excellent interfacial adhesion, biocompatibility, and low inflammatory response. This study opens the possibility for the development of insulation materials suitable for different types of electronics for neural engineering and other biomedical applications. Also important, GT analysis makes possible structural characterization of complex biological and biomimetic materials.

bioengineering↗

bioRxiv2019

Anti-biofilm Activity of Graphene Quantum Dots via Self-Assembly with Bacterial Amyloid Proteins

Bacterial biofilms represent an essential part of Earths ecosystem that can cause multiple ecological, technological and health problems. The environmental resilience and sophisticated organization of biofilms are enabled by the extracellular matrix that creates a protective network of biomolecules around the bacterial community. Current anti-biofilm agents can interfere with extracellular matrix production but, being based on small molecules, are degraded by bacteria and rapidly diffuse away from biofilms. Both factors severely reduce their efficacy, while their toxicity to higher organisms create additional barriers to their practicality. In this paper we report on the ability of graphene quantum dots to effectively disperse mature Staphylococcus aureus biofilms, interfering with the self-assembly of amyloid fibers - a key structural component of the extracellular matrix. Mimicking peptide-binding biomolecules, graphene quantum dots form supramolecular complexes with phenol soluble modulins, the peptide monomers of amyloid fibers. Experimental and computational results show that graphene quantum dots efficiently dock near the N-terminus of the peptide and change the secondary structure of phenol soluble modulins, which disrupts their fibrillation and represents a novel strategy for mitigation of bacterial communities. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/550285v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@a94402org.highwire.dtl.DTLVardef@b009b3org.highwire.dtl.DTLVardef@14cfb70org.highwire.dtl.DTLVardef@10f8e52_HPS_FORMAT_FIGEXP M_FIG GQD mediated staphylococcal biofilm dispersal. GQDs interact with PSM peptides and frustrate the fibrillation process. The reduction in amyloid fibers prevents robust stabilization of the biofilm. In addition, there is an increase in free monomeric and oligomeric PSM peptides which trigger dispersal events. C_FIG

bioengineering↗

bioRxiv2019

Chiroptical Kirigami Modulators for Terahertz Circular Dichroism Spectroscopy of Biomaterials

ABSTRACTSTerahertz circular dichroism (TCD) offers spectroscopic capabilities for understanding mesoscale chiral architecture and low-energy vibrations of macromolecules in (bio)materials1-5. However, the lack of dynamic polarization modulators comparable to polarization optics for other parts of electromagnetic spectrum impedes proliferation of TCD spectroscopy6-10. Here we show that tunable optical elements fabricated from patterned plasmonic sheets with periodic kirigami cuts make possible polarization modulation of THz radiation under application of mechanical strain. A herringbone pattern of microscale metal stripes enables dynamic range of polarization rotation modulation exceeding 80{degrees} over thousands of cycles. Upon out-of-plane buckling, the plasmonic stripes function as reconfigurable semi-helices of variable pitch aligned along the THz propagation direction. Several biomaterials, exemplified by elytrons of Chrysina gloriosa beetles, revealed distinct TCD fingerprints associated with the helical substructure in the biocomposite. Analogous kirigami modulators will also enable other applications in THz optics, such as polarization-based terahertz imaging and phase-encrypted telecommunication.

biophysics↗