DA Head

University of Leeds, Leeds, England, United Kingdom

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Publications (53)113.88 Total impact

  • Source
    P.D. Marsh · D.A. Head · D.A. Devine
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    ABSTRACT: Background The mouth supports a diverse microbiota which exists as structurally-organised biofilms on mucosal and dental surfaces. The oral microbiota provides major benefits to the host including: (a) colonisation resistance, (b) down-regulation of potentially damaging host inflammatory responses, and (c) active contributions to the normal development of the physiology of the mouth and the host defences. Highlight Generally, these communities live in harmony (symbiosis) with the host but, on occasions, this symbiotic relationship breaks down and disease occurs (dysbiosis). Disease is associated with shifts in the balance of the oral microbiota driven by changes in the local environment. These changes include more regular conditions of low pH in the biofilm, as a result of an altered diet or reduced saliva flow, thereby favouring the growth and metabolism of acidogenic and acid-tolerating bacteria, at the expense of beneficial oral micro-organisms, and increasing the risk of dental caries. The host mounts an inflammatory response if biofilm accumulates around the gingivae beyond levels compatible with health. If this fails to reduce the biomass, the altered environment selects for increased proportions of obligately anaerobic and proteolytic species that can subvert the host response leading, ultimately, to pocket formation and loss of attachment. Conclusion An appreciation of ecological principles can lead to new strategies for treatment by identifying and removing the factors that drive dysbiosis, while actively supporting the growth of the natural oral microbiota. Also, the beneficial activities of the resident oral microbiota are retained and the risk of dysbiosis is reduced.
    Full-text · Article · Aug 2015 · Journal of Oral Biosciences
  • Phil D. Marsh · David A. Head · Deirdre A. Devine
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    ABSTRACT: Humans have co-evolved with micro-organisms and have a symbiotic or mutualistic relationship with their resident microbiome. As at other body surfaces, the mouth has a diverse microbiota that grows on oral surfaces as structurally and functionally organised biofilms. The oral microbiota is natural and provides important benefits to the host, including immunological priming, down-regulation of excessive pro-inflammatory responses, regulation of gastrointestinal and cardiovascular systems, and colonisation by exogenous microbes. On occasions, this symbiotic relationship breaks down, and previously minor components of the microbiota outcompete beneficial bacteria, thereby increasing the risk of disease. Antimicrobial agents have been formulated into many oral care products to augment mechanical plaque control. A delicate balance is needed, however, to control the oral microbiota at levels compatible with health, without killing beneficial bacteria and losing the key benefits delivered by these resident microbes. These antimicrobial agents may achieve this by virtue of their recommended twice daily topical use, which results in pharmacokinetic profiles indicating that they are retained in the mouth for relatively long periods at sublethal levels. At these concentrations they are still able to inhibit bacterial traits implicated in disease (e.g. sugar transport/acid production; protease activity) and retard growth without eliminating beneficial species. In silico modelling studies have been performed which support the concept that either reducing the frequency of acid challenge and/or the terminal pH, or by merely slowing bacterial growth, results in maintaining a community of beneficial bacteria under conditions that might otherwise lead to disease (control without killing).
    No preview · Article · Apr 2015 · Caries Research
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    Philip D Marsh · David A Head · Deirdre A Devine
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    ABSTRACT: The mouth supports a diverse microbiota which provides major benefits to the host. On occasions, this symbiotic relationship breaks down (dysbiosis), and disease can be a consequence. We argue that progress in the control of oral diseases will depend on a paradigm shift away from approaches that have proved successful in medicine for many diseases with a specific microbial aetiology. Factors that drive dysbiosis in the mouth should be identified and, where possible, negated, reduced or removed, while antimicrobial agents delivered by oral care products may function effectively, even at sub-lethal concentrations, by modulating the activity and growth of potentially pathogenic bacteria. In this way, the beneficial activities of the resident oral microbiota will be retained and the risk of dysbiosis occurring will be reduced.
    Full-text · Article · Nov 2014 · Journal of Oral Microbiology
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    Leandro G. Rizzi · David A. Head · Stefan Auer
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    ABSTRACT: Above a critical concentration a wide variety of peptides and proteins self-assemble into amyloid fibrils which entangle to form percolating networks called hydrogels. Such hydrogels have important applications as biomaterials and in nanotechnology, but their applicability often depends on their mechanical properties for which we currently have no predictive capability. Here we use a peptide model to simulate the formation of amyloid fibril networks, and couple these to elastic network theory to determine their mechanical properties. The simulations reveal that the time-dependence of morphological quantities characterizing the network length scales can be collapsed onto master curves by using a time scaling function that depends on the interaction parameter between the peptides. The same scaling function is used to unveil a universal, non-monotonic dependence of the shear modulus with time. The obtained insight into the structure-function relationship between the peptide building blocks, network morphology and network mechanical properties can aid experimentalists to design amyloid fibril networks with tailored mechanical properties.
    Full-text · Article · Sep 2014 · Physical Review Letters
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    David A Head · Phil D Marsh · Deirdre A Devine
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    ABSTRACT: Dental caries or tooth decay is a prevalent global disease whose causative agent is the oral biofilm known as plaque. According to the ecological plaque hypothesis, this biofilm becomes pathogenic when external challenges drive it towards a state with a high proportion of acid-producing bacteria. Determining which factors control biofilm composition is therefore desirable when developing novel clinical treatments to combat caries, but is also challenging due to the system complexity and the existence of multiple bacterial species performing similar functions. Here we employ agent-based mathematical modelling to simulate a biofilm consisting of two competing, distinct types of bacterial populations, each parameterised by their nutrient uptake and aciduricity, periodically subjected to an acid challenge resulting from the metabolism of dietary carbohydrates. It was found that one population was progressively eliminated from the system to give either a benign or a pathogenic biofilm, with a tipping point between these two fates depending on a multiplicity of factors relating to microbial physiology and biofilm geometry. Parameter sensitivity was quantified by individually varying the model parameters against putative experimental measures, suggesting non-lethal interventions that can favourably modulate biofilm composition. We discuss how the same parameter sensitivity data can be used to guide the design of validation experiments, and argue for the benefits of in silico modelling in providing an additional predictive capability upstream from in vitro experiments.
    Full-text · Article · Aug 2014 · PLoS ONE
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    ABSTRACT: The cytoskeleton is a network of crosslinked, semiflexible filaments, and it has been suggested that it has properties of a glassy state. Here we employ optical-trap-based microrheology to apply forces to a model cytoskeleton and measure the high-bandwidth response at an anterior point. Simulating the highly nonlinear and anisotropic stress-strain propagation assuming affinity, we found that theoretical predictions for the quasistatic response of semiflexible polymers are only realized at high frequencies inaccessible to conventional rheometers. We give a theoretical basis for determining the frequency when both affinity and quasistaticity are valid, and we discuss with experimental evidence that the relaxations at lower frequencies can be characterized by the experimentally obtained nonaffinity parameter.
    No preview · Article · Apr 2014 · Physical Review E
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    ABSTRACT: The cytoskeleton is a network of crosslinked, semiflexible filaments, and it has been suggested that it has properties of a glassy state. Here we employ optical-trap-based microrheology to apply forces to a model cytoskeleton and measure the high-bandwidth response at an anterior point. Simulating the highly nonlinear and anisotropic stress-strain propagation assuming affinity, we found that theoretical predictions for the quasistatic response of semiflexible polymers are only realized at high frequencies inaccessible to conventional rheometers. We give a theoretical basis for determining the frequency when both affinity and quasistaticity are valid, and we discuss with experimental evidence that the relaxations at lower frequencies can be characterized by the experimentally obtained nonaffinity parameter.
    No preview · Article · Mar 2014 · Physical Review E
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    D A Head · W J Briels · Gerhard Gompper
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    ABSTRACT: In the presence of adenosine triphosphate, molecular motors generate active force dipoles that drive suspensions of protein filaments far from thermodynamic equilibrium, leading to exotic dynamics and pattern formation. Microscopic modeling can help to quantify the relationship between individual motors plus filaments to organization and dynamics on molecular and supramolecular length scales. Here, we present results of extensive numerical simulations of active gels where the motors and filaments are confined between two infinite parallel plates. Thermal fluctuations and excluded-volume interactions between filaments are included. A systematic variation of rates for motor motion, attachment, and detachment, including a differential detachment rate from filament ends, reveals a range of nonequilibrium behavior. Strong motor binding produces structured filament aggregates that we refer to as asters, bundles, or layers, whose stability depends on motor speed and differential end detachment. The gross features of the dependence of the observed structures on the motor rate and the filament concentration can be captured by a simple one-filament model. Loosely bound aggregates exhibit superdiffusive mass transport, where filament translocation scales with lag time with nonunique exponents that depend on motor kinetics. An empirical data collapse of filament speed as a function of motor speed and end detachment is found, suggesting a dimensional reduction of the relevant parameter space. We conclude by discussing the perspectives of microscopic modeling in the field of active gels.
    Full-text · Article · Mar 2014 · Physical Review E
  • Source
    D A Head
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    ABSTRACT: The sessile microbial communities known as biofilms exhibit varying architectures as environmental factors are varied, which for immersed biofilms includes the shear rate of the surrounding flow. Here we modify an established agent-based biofilm model to include affine flow and employ it to analyze the growth of surface roughness of single-species, three-dimensional biofilms. We find linear growth laws for surface geometry in both horizontal and vertical directions and measure the thickness of the active surface layer, which is shown to anticorrelate with roughness. Flow is shown to monotonically reduce surface roughness without affecting the thickness of the active layer. We argue that the rapid roughening is due to nonlocal surface interactions mediated by the nutrient field, which are curtailed when advection competes with diffusion. We further argue the need for simplified models to elucidate the underlying mechanisms coupling flow to growth.
    Preview · Article · Sep 2013 · Physical Review E
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    David A Head · Daisuke Mizuno
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    ABSTRACT: Analytical and numerical calculations are presented for the mechanical response of fiber networks in a state of axisymmetric prestress, in the limit where geometric nonlinearities such as fiber rotation are negligible. This allows us to focus on the anisotropy deriving purely from the nonlinear force-extension curves of individual fibers. The number of independent elastic coefficients for isotropic, axisymmetric, and fully anisotropic networks are enumerated before deriving expressions for the response to a locally applied force that can be tested against, e.g., microrheology experiments. Localized forces can generate anisotropy away from the point of application, so numerical integration of nonlinear continuum equations is employed to determine the stress field, and induced mechanical anisotropy, at points located directly behind and in front of a force monopole. Results are presented for the wormlike chain model in normalized forms, allowing them to be easily mapped to a range of systems. Finally, the relevance of these findings to naturally occurring systems and directions for future investigation are discussed.
    Preview · Article · Aug 2013 · Physical Review E
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    ABSTRACT: Forces are generated heterogeneously in living cells and transmitted through cytoskeletal networks that respond highly non-linearly. Here, we carry out high-bandwidth passive microrheology on vimentin networks reconstituted in vitro, and observe the nonlinear mechanical response due to forces propagating from a local source applied by an optical tweezer. Since the applied force is constant, the gel becomes equilibrated and the fluctuation-dissipation theorem can be employed to deduce the viscoelasticity of the local environment from the thermal fluctuations of colloidal probes. Our experiments unequivocally demonstrate the anisotropic stiffening of the cytoskeletal network behind the applied force, with greater stiffening in the parallel direction. Quantitative agreement with an affine continuum model is obtained, but only for the response at certain frequency ˜ 10-1000 Hz which separates the high-frequency power law and low-frequency elastic behavior of the network. We argue that the failure of the model at lower frequencies is due to the presence of non-affinity, and observe that zero-frequency changes in particle separation can be fitted when an independently-measured, empirical nonaffinity factor is applied.
    No preview · Article · Mar 2013
  • Source
    David A Head · Wj Briels · Gerhard Gompper
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    ABSTRACT: Robust self-organization of subcellular structures is a key principle governing the dynamics and evolution of cellular life. In fission yeast cells undergoing division, the mitotic spindle spontaneously emerges from the interaction of microtubules, motor proteins and the confining cell walls, and asters and vortices have been observed to self-assemble in quasi-two dimensional microtubule-kinesin assays. There is no clear microscopic picture of the role of the active motors driving this pattern formation, and the relevance of continuum modeling to filament-scale structures remains uncertain. Here we present results of numerical simulations of a discrete filament-motor protein model confined to a pressurised cylindrical box. Stable spindles, nematic configurations, asters and high-density semi-asters spontaneously emerge, the latter pair having also been observed in cytosol confined within emulsion droplets. State diagrams are presented delineating each stationary state as the pressure, motor speed and motor density are varied. We further highlight a parameter regime where vortices form exhibiting collective rotation of all filaments, but have a finite life-time before contracting to a semi-aster. Quantifying the distribution of life-times suggests this contraction is a Poisson process. Equivalent systems with fixed volume exhibit persistent vortices with stochastic switching in the direction of rotation, with switching times obeying similar statistics to contraction times in pressurised systems. Furthermore, we show that increasing the detachment rate of motors from filament plus-ends can both destroy vortices and turn some asters into vortices. We have shown that discrete filament-motor protein models provide new insights into the stationary and dynamical behavior of active gels and subcellular structures, because many phenomena occur on the length-scale of single filaments. Based on our findings, we argue the need for a deeper understanding of the microscopic activities underpinning macroscopic self-organization in active gels and urge further experiments to help bridge these lengths.
    Full-text · Article · Nov 2011 · BMC Biophysics
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    ABSTRACT: Dynamic networks designed to model the cellcytoskeleton can be reconstituted from filamentous actin, the motorproteinmyosin and a permanent cross-linker. They are driven out of equilibrium when the molecular motors are active. This gives rise to athermal fluctuations that can be recorded by tracking probe particles that are dispersed in the network. We have here probed athermal fluctuations in such “active gels” using video microrheology. We have measured the full distribution of probe displacements, also known as the van Hove correlation function. The dominant influence of thermal or athermal fluctuations can be detected by varying the lag time over which the displacements are measured. We argue that the exponential tails of the distribution derive from single motors close to the probes, and we extract an estimate of the velocity of motor heads along the actin filaments. The distribution exhibits a central Gaussian region which we assume derives from the action of many independent motorproteins far from the probe particles when athermal fluctuations dominate. Recording the whole distribution rather than just the typically measured second moment of probe fluctuations (mean-squared displacement) thus allowed us to differentiate between the effect of individual motors and the collective action of many motors.
    No preview · Article · Mar 2011 · Soft Matter
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    David A. Head · Gerhard Gompper · W. J. Briels
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    ABSTRACT: Active gels are a class of biologically-relevant material containing embedded agents that spontaneously generate forces acting on a sparse filament network. In vitro experiments of protein filaments and molecular motors have revealed a range of non- equilibrium pattern formation resulting from motor motion along filament tracks, and there are a number of hydrodynamic models purporting to describe such systems. Here we present results of extensive simulations designed to elucidate the microscopic basis underpinning macroscopic flow in active gels. Our numerical scheme includes thermal fluctuations in filament positions, excluded volume interactions, and filament elasticity in the form of bending and stretching modes. Motors are represented individually as bipolar springs governed by rate-based rules for attachment, detachment and unidirectional motion of motor heads along the filament contour. We systematically vary motor density and speed, and uncover parameter regions corresponding to unusual statics and dynamics which overlap but do not coincide. The anomalous statics arise at high motor densities and take the form of end-bound localized filament bundles for rapid motors, and extended clusters exhibiting enhanced small-wavenumber density fluctuations and power-law cluster-size distributions for slow, processive motors. Anomalous dynamics arise for slow, processive motors over a range of motor densities, and are most evident as superdiffusive mass transport, which we argue is the consequence of a form of effective self-propulsion resulting from the polar coupling between motors and filaments. Comment: 14 pages, 17 figures. Submitted to Soft Matter
    Full-text · Article · Sep 2010 · Soft Matter
  • D. A. Head · Hajime Tanaka
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    ABSTRACT: A system far from equilibrium is characterized by unconventional many-body dynamical effects, which can lead to anomalous density fluctuations and mass transport. Interestingly, these structural and dynamic features often emerge simultaneously in driven dissipative systems. Here we seek an origin of their co-existence by numerical simulations of a two-dimensional, driven system of inelastic particles without external damping terms. We reveal a causal link between superdiffusive transport and giant density fluctuations. The kinetic dissipation upon particle collisions depends on the relative velocity of colliding particles, and is responsible for the self-generated large-scale persistent directional motion of particles that underlies the link between structure and transport. This scenario is supported by a simple scaling argument.
    No preview · Article · Aug 2010 · EPL (Europhysics Letters)
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    D A Head · D Mizuno
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    ABSTRACT: Many active materials and biological systems are driven far from equilibrium by embedded agents that spontaneously generate forces and distort the surrounding material. Probing and characterizing these athermal fluctuations are essential to understand the properties and behaviors of such systems. Here we present a mathematical procedure to estimate the local action of force-generating agents from the observed fluctuating displacement fields. The active agents are modeled as oriented force dipoles or isotropic compression foci, and the matrix on which they act is assumed to be either a compressible elastic continuum or a coupled network-solvent system. Correlations at a single point and between points separated by an arbitrary distance are obtained, giving a total of three independent fluctuation modes that can be tested with microrheology experiments. Since oriented dipoles and isotropic compression foci give different contributions to these fluctuation modes, ratiometric analysis allows us characterize the force generators. We also predict and experimentally find a high-frequency ballistic regime, arising from individual force-generating events in the form of the slow buildup of stress followed by rapid but finite decay. Finally, we provide a quantitative statistical model to estimate the mean filament tension from these athermal fluctuations, which leads to stiffening of active networks.
    Preview · Article · Apr 2010 · Physical Review E
  • Source
    David A. Head · Hajime Tanaka
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    ABSTRACT: A system far from equilibrium is characterized by unconventional many-body dynamical effects, which can lead to anomalous density fluctuations and mass transport. Interestingly, these structural and dynamic features often emerge simultaneously in driven dissipative systems. Here we seek an origin of their co-existence by numerical simulations of a two-dimensional driven granular gas. We reveal a causal link between superdiffusive transport and giant density fluctuations. The kinetic dissipation upon particle collisions depends on the relative velocity of colliding particles, and is responsible for the self-generated large-scale persistent directional motion of particles that underlies the link between structure and transport. This scenario is supported by a simple scaling argument. Comment: 4 pages, 4 figures + 1 table
    Preview · Article · Mar 2010
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    David A Head
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    ABSTRACT: We conduct athermal simulations of freely cooling, viscous soft spheres around the jamming transition density varphi(J) and find evidence for a growing length xi(t) that governs relaxation to mechanical equilibrium. xi(t) is manifest in both the velocity correlation function and the spatial correlations in a scalar measure of local force balance which we define. Data for different densities varphi can be collapsed onto two master curves by scaling xi(t) and t by powers of |varphi-varphi(J)|, indicative of critical scaling. Furthermore, particle transport for varphi>varphi(J) exhibits aging and superdiffusion similar to a range of soft matter experiments, suggesting a common origin. Finally, we explain how xi(t) at late times maps onto known behavior away from varphi(J).
    Preview · Article · May 2009 · Physical Review Letters
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    ABSTRACT: Cells actively probe mechanical properties of their environment by exerting internally generated forces. The response they encounter profoundly affects their behavior. Here we measure in a simple geometry the forces a cell exerts suspended by two optical traps. Our assay quantifies both the overall force and the fraction of that force transmitted to the environment. Mimicking environments of varying stiffness by adjusting the strength of the traps, we found that the force transmission is highly dependent on external compliance. This suggests a calibration mechanism for cellular mechanosensing.
    Full-text · Article · May 2009 · Physical Review Letters
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    ABSTRACT: Quantitatively measuring the mechanical properties of soft matter over a wide range of length and time scales, especially if a sample is as complex as typical biological materials, remains challenging. Living cells present a further complication because forces are generated within these nonequilibrium materials that can change material properties. We have here developed high-bandwidth techniques for active one- and two-particle microrheology to tackle these issues. By combining active micromanipulation of probe particles with an optical trap with high-resolution tracking of thermal motions of the very same particles by laser interferometry, we can both measure the mechanical properties of and, at the same time, identify nonequilibrium forces in soft materials. In both simple liquids and equilibrium cytoskeletal actin networks, active microrheology (AMR) proves to be less noise sensitive than and offers extended bandwidth (0.1−100 kHz) compared to passive microrheology (PMR), which merely tracks thermal motions. We confirm high-frequency power-law dynamics in equilibrium actin networks with two-particle AMR and also discuss low-frequency local mechanical response near probe particles which shows up in one-particle AMR. The combination of AMR and PMR allowed us to quantify nonthermal force fluctuations in actin networks driven by myosin motor proteins. Our approach offers a new direct way to investigate the nonequilibrium dynamics of living materials.
    Preview · Article · Sep 2008 · Macromolecules

Publication Stats

1k Citations
113.88 Total Impact Points

Institutions

  • 2011-2015
    • University of Leeds
      • School of Computing
      Leeds, England, United Kingdom
  • 2011-2014
    • Forschungszentrum Jülich
      • Theoretical Soft Matter and Biophysics (ICS-2 / IAS-2)
      Jülich, North Rhine-Westphalia, Germany
  • 2010
    • Universiteit Twente
      Enschede, Overijssel, Netherlands
  • 2006-2010
    • The University of Tokyo
      • • Institute of Industrial Science
      • • Department of Applied Physics
      Tokyo, Tokyo-to, Japan
  • 2002-2006
    • VU University Amsterdam
      • Department of Physics and Astronomy
      Amsterdam, North Holland, Netherlands
  • 1999-2002
    • The University of Edinburgh
      • School of Physics and Astronomy
      Edinburgh, SCT, United Kingdom
  • 1996-1998
    • Brunel University London
      अक्सब्रिज, England, United Kingdom