Peter G Petrov

University of Exeter, Exeter, England, United Kingdom

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Publications (17)61.77 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Alpha-tocopherol (Vitamin E) has attracted considerable attention as a potential protective or palliative agent. In vitro its free-radical scavenging antioxidant action has been widely demonstrated. In vivo, however, vitamin E treatment exhibits negligible benefits against oxidative stress. Alpha-tocopherol influences lipid ordering within biological membranes and its derivatives have been suggested to inhibit the multi-drug efflux pump P-glycoprotein. This study employs the fluorescent membrane probe Di-8-ANEPPS to investigate whether these effects are connected via influences on the membrane dipole potential (MDP), an intrinsic property of biological membranes previously demonstrated to modulate P-glycoprotein activity. Alpha-tocopherol and its non free-radical scavenging succinate analogue induced similar decreases in the MDP of phosphatidylcholine vesicles. Alpha-tocopherol succinate also reduced the MDP of T-lymphocytes subsequently decreasing the binding affinity of Saquinavir for P-glycoprotein. Additionally, alpha-tocopherol succinate demonstrated a preference for cholesterol treated (membrane microdomain enriched) cells over membrane cholesterol-depleted cells. Microdomain disruption via cholesterol depletion decreased Saquinavir affinity for P-glycoprotein, potentially implicating these structures in the influence of alpha-tocopherol succinate on P-glycoprotein. This study provides evidence of a microdomain dipole potential-dependent mechanism by which alpha-tocopherol analogues influence P-glycoprotein activity. These findings have implications for the use of alpha-tocopherol derivatives for drug delivery across biological barriers. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    The Journal of Lipid Research 05/2015; DOI:10.1194/jlr.M059519 · 4.73 Impact Factor
  • Critical Care 03/2013; 17(2). DOI:10.1186/cc11949 · 5.04 Impact Factor
  • Critical Care 03/2013; 17(2). DOI:10.1186/cc11950 · 5.04 Impact Factor
  • S.A. Jewell, P G Petrov, C P Winlove
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    ABSTRACT: The membrane dipole potential (ψ(d)) is an important biophysical determinant of membrane function and a sensitive indicator of lipid organisation. In this study we have used the environmentally sensitive probe di-8-anepps to explore the effects of oxidative stress on the membrane dipole potential of human erythrocytes. Cells suspended in 0.15mM phosphate buffered saline containing 0.1mg/ml albumin maintained a mean value for ψ(d) of 270 (± 20) mV over the course of 1hour. In the presence of 0.4mM cumene hydroperoxide there was an increase in ψ(d) of 14 (± 7) %, accompanied by a decrease in cell diameter of~14 (± 2) % . Exposure of the cells to 0.4mM hydrogen peroxide caused ψ(d) to decrease by 13 (± 8) % at the centre of the cell and 8 (± 5) % at the edge whilst the diameter remained constant. In both cases the changes were equivalent to a change in transmembrane electric field of a magnitude of~10 MVm(-1), sufficient to influence membrane function. Raman microspectrometry supported the conclusion that cumene exerts its effect primarily on membrane lipids whilst hydrogen peroxide causes the formation of spectrin-haemoglobin complexes which stiffen the membrane.
    Biochimica et Biophysica Acta 01/2013; 1828(4). DOI:10.1016/j.bbamem.2012.12.019 · 4.66 Impact Factor
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    ABSTRACT: This paper considers the dynamics of a microscale swimmer based on two magnetic beads that are elastically coupled together. A time-varying external magnetic field is imposed that has two principal effects: one is to exert a torque on the magnetic beads. The second is to change the orientation of the magnetic field dipoles in one or both beads, depending on their ferromagnetic properties. This then creates an attraction or repulsion between the two dipoles. The combination of dipole attraction/repulsion, moderated by the elastic coupling, and torque gives motions that are not generally time reversible and can lead to unidirectional swimming, that is persistent motion in one direction, in a Stokes flow regime. The equations of motion for the swimmer are set up using a Lagrangian formulation and supplemented by equations giving the dipole orientation of the magnetic fields of the beads in the external field. The equations are non-dimensionalized and key parameters determined. Numerical simulations reveal a number of regimes that are studied using simplified models and multiple scale analysis. Approximate thresholds are obtained above which the swimmer moves in a closed path and below which the orientation is ‘trapped’ giving unidirectional motion. Three mechanisms for such trapping are isolated and discussed.
    The Quarterly Journal of Mechanics and Applied Mathematics 01/2012; 64(3). DOI:10.1093/qjmam/hbr012 · 0.57 Impact Factor
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    ABSTRACT: This paper concerns the interaction of several ferromagnetic microswimmers, their motion and the resulting fluid mixing. Each swimmer consists of two ferromagnetic beads joined by an elastic link, and is driven by an external, time-dependent magnetic field. The external field provides a torque on a swimmer and, together with the varying attraction between the magnetic beads, generates a time-irreversible motion leading to persistent swimming in a low Reynolds number environment. The aim of the present paper is to consider the interactions between several swimmers. A regime is considered in which identical swimmers move in the same overall direction, and their motion is synchronised because of driving by the external field. It is found that two swimmers tend to encircle one another while three undergo more complicated motion that may involve the braiding of swimmer trajectories. By means of approximations it is established that the interaction between pairs of swimmers gives circulatory motion which falls off with an inverse square law and is linked to their overall speed of motion through the fluid. As groups of two or more swimmers move through the fluid they process fluid, leaving behind a trail of fluid that has undergone mixing: this is investigated by following streak lines numerically.
    The European Physical Journal E 11/2011; 34(11):121. DOI:10.1140/epje/i2011-11121-9 · 2.18 Impact Factor
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    John P Hale, C Peter Winlove, Peter G Petrov
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    ABSTRACT: We investigate the effect of oxidative stress on red blood cell membrane mechanical properties in vitro using detailed analysis of the membrane thermal fluctuation spectrum. Two different oxidants, the cytosol-soluble hydrogen peroxide and the membrane-soluble cumene hydroperoxide, are used, and their effects on the membrane bending elastic modulus, surface tension, strength of confinement due to the membrane skeleton, and 2D shear elastic modulus are measured. We find that both oxidants alter significantly the membrane elastic properties, but their effects differ qualitatively and quantitatively. While hydrogen peroxide mainly affects the elasticity of the membrane protein skeleton (increasing the membrane shear modulus), cumene hydroperoxide has an impact on both membrane skeleton and lipid bilayer mechanical properties, as can be seen from the increased values of the shear and bending elastic moduli. The biologically important implication of these results is that the effects of oxidative stress on the biophysical properties, and hence the physiological functions, of the cell membrane depend on the nature of the oxidative agent. Thermal fluctuation spectroscopy provides a means of characterizing these different effects, potentially in a clinical milieu.
    Biophysical Journal 10/2011; 101(8):1921-9. DOI:10.1016/j.bpj.2011.08.053 · 3.83 Impact Factor
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    ABSTRACT: Calreticulin (CRT) is an endoplasmic reticulum (ER) chaperone responsible for glycoprotein folding and Ca(2+) homeostasis. CRT also has extracellular functions, e.g. tumor and apoptotic cell recognition and wound healing, but the mechanism of CRT extracellular release is unknown. Cytosolic localization of CRT is determined by signal peptide and subsequent retrotranslocation of CRT into the cytoplasm. Here, we show that under apoptotic stress conditions, the cytosolic concentration of CRT increases and associates with phosphatidylserine (PS) in a Ca(2)(+)-dependent manner. PS distribution is regulated by aminophospholipid translocase (APLT), which maintains PS on the cytosolic side of the cell membrane. APLT is sensitive to redox modifications of its SH groups by reactive nitrogen species. During apoptosis, both CRT expression and the concentration of nitric oxide (NO) increase. By using S-nitroso-l-cysteine-ethyl-ester, an intracellular NO donor and inhibitor of APLT, we showed that PS and CRT externalization occurred together in an S-nitrosothiol-dependent and caspase-independent manner. Furthermore, the CRT and PS are relocated as punctate clusters on the cell surface. Thus, CRT induced nitrosylation and its externalization with PS could explain how CRT acts as a bridging molecule during apoptotic cell clearance.
    Journal of Molecular Biology 09/2010; 401(5):799-812. DOI:10.1016/j.jmb.2010.06.064 · 3.96 Impact Factor
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    ABSTRACT: We study the mechanical properties of ternary lipid bilayers assembled in giant vesicles, formed from a saturated and an unsaturated phosphocholine (in equal proportions) and cholesterol. As a function of temperature, these systems can undergo in-plane phase separation. Using image analysis we identify the vesicle contour, and quantify the vesicle shape and the amplitude of membrane thermal fluctuations. The two lipid compositions chosen show different thermotropic behaviours. At 60 mol% cholesterol the membrane is in a uniform liquid state over the entire temperature range investigated (10-50 °C), but vesicles containing 30 mol% cholesterol undergo phase separation into two immiscible liquid phases at around 28 °C. Upon cooling below this transition temperature we observe a marked increase in the measured bending elastic modulus. Phase separation proceeds over a long time (tens of minutes), and we measure the properties of vesicles both during the domain coarsening phase and in the fully phase separated condition. Fluorescence microscopy allows us to identify the coexisting phases. We can therefore measure directly the bending moduli of each of the phases as a function of temperature, showing a strong variation which is attributed to the changing phospholipid and cholesterol composition.
    Journal of Physics Condensed Matter 02/2010; 22(6):062101. DOI:10.1088/0953-8984/22/6/062101 · 2.22 Impact Factor
  • Feodor Y. Ogrin, Peter G. Petrov, C. Peter Winlove
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    ABSTRACT: A Reply to the Comment by Andrej Vilfan and Holger Stark.
    Physical Review Letters 11/2009; 103(19). DOI:10.1103/PhysRevLett.103.199802 · 7.73 Impact Factor
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    ABSTRACT: We outline a new method of analysis of thermal shape fluctuations of red blood cells, based on comparison between experiments and coarse-grained molecular dynamics simulations. The fluctuations of 2D equatorial contours of red blood cells are recorded experimentally using fast phase-contrast video microscopy, from which the fluctuation spectrum is calculated. The spectrum is compared to the corresponding contour fluctuation spectrum obtained from a finite-temperature particle-dynamics simulation, modelling a cell with bending and shear elasticity and conserved volume and surface area. We demonstrate that the simulation correctly describes the mean cell shape as well as the membrane thermal fluctuations, returning physically sound values for the relevant membrane elastic moduli.
    Soft Matter 09/2009; 5(19):3603-3606. DOI:10.1039/b910422d · 4.15 Impact Factor
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    Feodor Y Ogrin, Peter G Petrov, C Peter Winlove
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    ABSTRACT: We propose a model for a novel artificial low Reynolds number swimmer, based on the magnetic interactions of a pair of ferromagnetic particles: one with hard and the other with soft magnetic properties, connected by a linear spring. Using a computational model, we analyze the behavior of the system and demonstrate that for realistic values of the parameters involved, the swimmer is capable of self-propelling with average speeds of the order of hundreds of micrometers per second.
    Physical Review Letters 05/2008; 100(21):218102. DOI:10.1103/PhysRevLett.100.218102 · 7.73 Impact Factor
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    ABSTRACT: We investigate the effect of the skeletal protein spectrin on the lateral order in dipalmitoyl phosphatidylserine monolayers spread on aqueous surfaces using grazing incidence X-ray diffraction. Without spectrin, the condensed lipid monolayer exhibits two-dimensional hexagonal packing, characterized by monotonic decrease in the d-spacing and increase in the degree of order with increasing surface pressure between 17 and 36 mN/m. Addition of spectrin to the aqueous subphase at high pressures preserves the monolayers structural parameters unchanged from 36 to 25 mN/m. These results demonstrate for the first time that spectrin could participate in sustaining the two-dimensional order in lipid domains through a direct interaction with phosphatidylserine species.
    Chemistry and Physics of Lipids 02/2008; 151(1):66-8. DOI:10.1016/j.chemphyslip.2007.09.003 · 2.59 Impact Factor
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    ABSTRACT: We report a grazing incidence x-ray diffraction (GIXD) investigation of the surface lipid layer of the pre-ocular tear film. For the first time we demonstrate the existence of 2D order over a wide range of surface pressures in this system, with typical spicing of 3.75A and 4.16A independent of the monolayer surface pressure. Analogous lipid ordering is also found in an artificial lipid mixture of the major lipid components of the tear film, suggesting that the 2D ordering is set by generic lipid-lipid interactions. Fluorescence microscopy of the natural and artificial tear film mixture reveals the co-existence of a dilute and a much more condensed phase in the amphiphilic lipid matrix over the pressure range of 15-45mN/m investigated by GIXD, plus an additional structure due to the much more hydrophobic part of the mixture. This evidence supports the previous hypothesis that tear film has a layered structure.
    Experimental Eye Research 07/2007; 84(6):1140-6. DOI:10.1016/j.exer.2007.02.012 · 3.02 Impact Factor
  • Radiation Physics and Chemistry 10/2004; 71(3):959-960. DOI:10.1016/j.radphyschem.2004.05.027 · 1.19 Impact Factor
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    Pietro Cicuta, Ian Hopkinson, Peter G Petrov
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    ABSTRACT: We report a method to control the conformation of a weak polyampholyte (the protein $\beta$-casein) in Langmuir monolayers by light, even though the protein is not photosensitive. Our approach is to couple the monolayer state to a photochemical reaction excited in the liquid subphase. The conformational transition of the protein molecule is triggered through its sensitivity to a subphase bulk field (pH in this study), changing in the course of the photochemical process. Thus, reaction of photoaquation of the ferrocyanide ion, which increases the subphase pH from 7.0 to about 8.3, produces a change in the surface monolayer pressure, $\Delta\Pi$, between -0.5 and +1.5 ${\rm mN/m}$ (depending on the surface concentration), signalling a conformational switch. The approach proposed here can be used to selectively target and influence different interfacial properties by light, without embedding photosensitisers in the matrix. Comment: 5 pages, revtex4, to be published in J.Chem.Phys
    The Journal of Chemical Physics 10/2001; 115(21). DOI:10.1063/1.1423666 · 3.12 Impact Factor

Publication Stats

90 Citations
61.77 Total Impact Points


  • 2007–2015
    • University of Exeter
      Exeter, England, United Kingdom
  • 2001
    • University of Cambridge
      • Department of Physics: Cavendish Laboratory
      Cambridge, ENG, United Kingdom