Papers by Pavel Bashkirov
Noise in Ultrashort Elastic Membrane Nanotube
Biochemistry (Moscow). Supplement. Series A, Membrane and cell biology, Dec 1, 2022
Biochemistry (Moscow). Supplement. Series A, Membrane and cell biology, Jul 1, 2017
⎯Amphipathic alpha-helical peptides are perspective antimicrobial drugs. These peptides are parti... more ⎯Amphipathic alpha-helical peptides are perspective antimicrobial drugs. These peptides are partially embedded into the membrane to a shallow depth so that the longitudinal axis of the helix is parallel to the plane of the membrane or deviates from it by a small angle. In the framework of theory of elasticity of liquid crystals, adapted to lipid membranes, we calculated the energy of deformations occurring near the peptides partially embedded into the membrane. The energy of deformations is minimal when two peptides are parallel to each other and stay at a distance of about 5 nm. This configuration is stable with respect to small parallel displacements of the peptides and with respect to small variation of the angle between their axes both in the plane of the membrane and in the perpendicular direction. As a result of deformation the average thickness of the membrane decreases. The distribution of the elastic energy density has a maximum in the middle between the peptides. This region is the most likely place for formation of the through pores in the membrane. Since the equilibrium distance between the peptides is relatively large, it is assumed that the originally appearing pore should be purely lipidic.
European journal of medicinal chemistry, Oct 1, 2019
The rise of antibiotic resistance has necessitated the development of alternative strategies for ... more The rise of antibiotic resistance has necessitated the development of alternative strategies for the treatment of infectious diseases. Antimicrobial peptides (AMPs), components of the innate immune response in various organisms, are promising next-generation drugs against bacterial infections. The ability of the medicinal leech Hirudo medicinalis to store blood for months with little change has attracted interest regarding the identification of novel AMPs in this organism. In this study, we employed computational algorithms to the medicinal leech genome assembly to identify amino acid sequences encoding potential AMPs. Then, we synthesized twelve candidate AMPs identified by the algorithms, determined their secondary structures, measured minimal inhibitory concentrations against three bacterial species (Escherichia coli, Bacillus subtilis, and Chlamydia thrachomatis), and assayed cytotoxic and haemolytic activities. Eight of twelve candidate AMPs possessed antimicrobial activity, and only two of them, 3967 (FRIMRILRVLKL) and 536-1 (RWRLVCFLCRRKKV), exhibited inhibition of growth of all tested bacterial species at a minimal inhibitory concentration of 10 micromoles. Thus, we evidence the utility of the developed computational algorithms for the identification of AMPs with low toxicity and haemolytic activity in the medicinal leech genome assembly.
Annual Review of Biophysics, May 9, 2022
The Relationship of a Person's Resilience with His Temperament and the Level of Experiencing Stressful Situations of Various Genesis
Институт психологии Российской академии наук. Организационная психология и психология труда
Non-toxic antimicrobial peptide Hm-AMP2 from leech metagenome proteins identified by the gradient-boosting approach
Materials & Design
Oxidative stress and ROS are important players in the pathogenesis of several diseases. Besides t... more Oxidative stress and ROS are important players in the pathogenesis of several diseases. Besides the direct modification of proteins, ROS modify lipids with negative spontaneous curvature, such as phosphatidylethanolamine (PE), producing PE adducts and lysolipids. The formation of PE-adducts potentiates the protonophoric activity of the uncoupling protein 1 (UCP1), but the molecular mechanism remains obscure. Here, we connected the ROS-mediated lipid shape alteration with the membrane mechanical properties and function of UCP1 and adenine nucleotide translocase 1 (ANT1). We found that lysophosphatidylcholines (OPC and MPC) and PE adducts decrease a bending modulus in lipid bilayers and increase the protonophoric activity of both proteins. Furthermore, MD simulations revealed that modified PEs and lysolipids alter the membrane lateral pressure profile in the same direction and range, indicating that modified PEs act as lipids with positive spontaneous curvature. Both results indicate ...
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology, 2017
⎯Theoretical model of a through pore formation in lipid bilayer membrane under applied lateral te... more ⎯Theoretical model of a through pore formation in lipid bilayer membrane under applied lateral tension was developed. In the framework of elastic theory of liquid crystals adapted to lipid membranes, we calculated a continuous trajectory from intact bilayer through a hydrophobic defect to a through pore. It was shown that the major energetic characteristic of membrane stability with respect to the pore formation, i. e., line tension, depends both on the pore radius and on the value of the applied lateral tension. This leads to a non-monotonous dependence of the average waiting time of the pore formation on the lateral tension: at low tensions the waiting time was large, then there was a local minimum, after which the average waiting time was increasing again. For membranes formed from stearoyl oleoyl phosphatidylcholine, the local minimum corresponded to the lateral tension of 7 mN/m; the calculated value of the edge line tension of a large pore was 16.5 pN. These results are consistent with available experimental data.
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology, 2017
⎯Investigation of the transport phenomena in the nanoscopic channels/pores with the diameter smal... more ⎯Investigation of the transport phenomena in the nanoscopic channels/pores with the diameter smaller than 100 nm is of utmost importance for various biological, medical, and technical applications. Presently, the main line of development of nanofluidics is creation of biosensors capable of detecting single molecules and manipulating them. Detection of molecules is based on the measurement of electric current through a channel of appropriate size: when the molecule enters the channel, which diameter is comparable with the molecule size, the ion current reduces. In order to improve transport properties of such channels, their walls are often coated with a lipid bilayer, which behaves as two-dimensional liquid and thus is capable of supporting transport phenomena. In the present work, we utilized this property of lipid membranes for the development of a method for detecting and controlling transport of single-stranded DNA through channels formed by membrane cylinders with the luminal radii of 5-7 nm. We have demonstrated that in the conditions of small ion strength, the appearance of a DNA molecule inside such channel is accompanied by an increase of its ion conductivity and can be controlled by the polarity of the applied voltage. The amplitude of the ion current increase allows evaluating the amount of DNA molecules inside the channels. It was also demonstrated that upon adsorption of DNA molecules on the lipid bilayer surface, the membrane cylinder behaves as a voltage-sensitive selective ion channel.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2021
Membrane nanotubes (NTs) and their networks play an important role in intracellular membrane tran... more Membrane nanotubes (NTs) and their networks play an important role in intracellular membrane transport and intercellular communications. The transport characteristics of the NT lumen resemble those of conventional solid-state nanopores. However, unlike the rigid pores, the soft membrane wall of the NT can be deformed by forces driving the transport through the NT lumen. This intrinsic coupling between the NT geometry and transport properties remains poorly explored. Using synchronized fluorescence microscopy and conductance measurements, we revealed that the NT shape was changed by both electric and hydrostatic forces driving the ionic and solute fluxes through the NT lumen. Far from the shape instability, the strength of the force effect is determined by the lateral membrane tension and is scaled with membrane elasticity so that the NT can be operated as a linear elastic sensor. Near shape instabilities, the transport forces triggered large-scale shape transformations, both stochastic and periodic. The periodic oscillations were coupled to a vesicle passage along the NT axis, resembling peristaltic transport. The oscillations were parametrically controlled by the electric field, making NT a highly nonlinear nanofluidic circuitry element with biological and technological implications.
Biophysical Journal, 2017
Biophysical Journal, 2016
Biophysical Journal, 2014
The rigidity of lipid bilayer, the structural core of all cellular membranes, is one of the key f... more The rigidity of lipid bilayer, the structural core of all cellular membranes, is one of the key force factor in membrane remodeling. For most of ''biomimetic'' lipid compositions the rigidity is thought to be only a weak function of the composition. However, for multicomponent membranes the composition is coupled to geometry, resulting in lateral redistribution of components in curvature gradients. Such redistribution can substantially facilitate local membrane deformations. We detected that such a decrease of apparent membrane rigidity in pure lipid bilayers containing physiological amounts of dioleoylphosphotidylethanolamin (DOPE), the lipid characterized by highly negative intrinsic curvature. Analyzing fast shape transformations of membrane nanotubes containing different amounts of DOPE we found that the membrane softening followed concentration-dependent redistribution of DOPE towards negative membrane curvature. The apparent bending rigidity of DOPE-containing membranes decreased almost twofold at 30mol% of DOPE, indicating that similar amount of DOPE in cellular membranes can substantially facilitate deformations.
Biophysical Journal, 2014
(62%), but the remaining 38% of digestion occurred in the course of the subsequent intermittent e... more (62%), but the remaining 38% of digestion occurred in the course of the subsequent intermittent encounters. The complex formation was maintained after the DNA break. This is suggestive of an intrinsic behaviour in which the DNA and protein molecules are continuously held together by switching their binding positions with short-range interactions. It also provides a clue to understanding an efficient and effective reaction by the DNA-binding proteins in bacterial cells.
Cell, 2008
The GTPase dynamin is critically involved in membrane fission during endocytosis. How does dynami... more The GTPase dynamin is critically involved in membrane fission during endocytosis. How does dynamin use the energy of GTP hydrolysis for membrane remodeling? By monitoring the ionic permeability through lipid nanotubes (NT), we found that dynamin was capable of squeezing NT to extremely small radii, depending on the NT lipid composition. However, long dynamin scaffolds did not produce fission: instead, fission followed GTPase-dependent cycles of assembly and disassembly of short dynamin scaffolds and involved a stochastic process dependent on the curvature stress imposed by dynamin. Fission happened spontaneously upon NT release from the scaffold, without leakage. Our calculations revealed that local narrowing of NT could induce cooperative lipid tilting, leading to self-merger of the inner monolayer of NT (hemifission), consistent with the absence of leakage. We propose that dynamin transmits GTP's energy to periodic assembling of a limited curvature scaffold that brings lipids to an unstable intermediate.
Biophysical Journal, 2013
Biophysical Journal, 2009
In this study, the center-of-mass diffusion and shape fluctuations of large unilamellar 1-palmito... more In this study, the center-of-mass diffusion and shape fluctuations of large unilamellar 1-palmitoyl-2-oleyl-sn-glycero-phosphatidylcholine vesicles prepared by extrusion are studied by means of neutron spin echo in combination with dynamic light scattering. The intermediate scattering functions were measured for several different values of the momentum transfer, q, and for different cholesterol contents in the membrane. The combined analysis of neutron spin echo and dynamic light scattering data allows calculation of the bending elastic constant, k, of the vesicle bilayer. A stiffening effect monitored as an increase of k with increasing cholesterol molar ratio is demonstrated by these measurements.
16S rRNA gene sequencing data of the upper respiratory tract microbiome in the SARS-CoV-2 infected patients
Data in Brief
Protein-Lipid Interactions: Perspectives, Techniques and Challenges
Biophysical Journal, Feb 1, 2018
Non-lamellar lipid phases such as the inverted hexagonal (HII) phase are of special interest in n... more Non-lamellar lipid phases such as the inverted hexagonal (HII) phase are of special interest in nanomedicine, e.g. in the drug/gene release step of intracellular therapeutic delivery to the target cell. In this study, the structural properties, including the deuterium order parameters and lattice distance, of DOPE lipids in the HII phase were studied as a function of temperature using molecular dynamics (MD) simulation, NMR, and SAXS experiments. MD simulation was also used to provide deeper insights into the effect of water per lipid (WPL) and salt concentration on both structural and dynamical properties of DOPE and POPE systems in HII phase. The preliminary results suggest that the WPL has a high impact on both deuterium order parameter and lattice distance. In principle, to be consistent and comparable with experimental data, the WPL in the simulation should be the same to the one in the corresponding experimental setup. However, the accurate measurement of the WPL inside the water channels of the HII phase is challenging experimentally since it requires the experiments to be conducted in the low WPL regime. Given well-established force field parameters for the lipids, which is the case for both DOPE and POPE lipids, computer simulation can assist experimentalists in estimating the WPL. In addition, this will provide a methodology for lipid force field parameter development in situations where only experimental data in the HII phase are available for that specific lipid. Finally, since experimental data for DOPE and POPE lipids in the HII phase is available, these systems can form frameworks to validate the simulation setup for HII systems required for the study of other lipids or lipid mixtures in this phase.
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Papers by Pavel Bashkirov