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Cell adhesion century: culture breakthrough

Event

Starts:

April
282014

09:00

Ends:

April
292014

17:00

Location

The Royal Society, London, 6-9 Carlton House Terrace, London, SW1Y 5AG

Overview

 

Cell adhering to glass; actin cytoskeleton in red, focal adhesion contacts in green and yellow (permission F Rehfeldt)

Scientific discussion meeting organised by Professor Kevin Kendall FRS, Professor Stephen Busby FRS, Professor Costantino Creton, Dr Florian Rehfeldt and Professor Gabriel Waksman FRS

Event details

This meeting celebrates the 100th anniversary of the discovery that cells require adhesion to a solid surface to grow outside the animal organ. As new culturing techniques now allow organ growth in the laboratory, it is timely to discuss cell adhesion in relation to implantation, cancer, tooth decay, parasitic diseases, bacteria, virus attack, nanoparticle toxicity, theory, computer modelling, ethics and many related topics. The outcomes will impact across all scientific disciplines.

Biographies of the organisers and speakers are available below. Recorded audio of the presentations will be available on this page after the event and the papers will be published in a future issue of Philosophical Transactions B.

Download meeting programme.

This meeting is immediately followed by a related satellite meeting at the Royal Society at Chicheley Hall, home of the Kavli Royal Society International Centre.

Attending this event

This event is intended for researchers in relevant fields and is free to attend. There are a limited number of places and registration is essential. An optional lunch is offered and should be booked during registration (all major credit cards accepted).

Enquiries: Contact the events team

Event organisers

Select an organiser for more information

Schedule of talks

Session 1: van der Waals adhesion influencing organisms

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Chair: Professor Kevin Kendall FRS

van der Waals forces

Professor Kevin Kendall FRS, Chemical Engineering, University of Birmingham, UK

Abstract

Adhesion molecules have been thought to control the adhesion of cells [1]. Unfortunately, the ‘lock and key’ model is unacceptable. While there is no doubt that a coating of adhesion molecules such as fibronectin on a surface affects cell adhesion, this is only one factor in the equation. Van der Waals force is the key cause of cell adhesion and is purely electromagnetic. Substrate elasticity and geometry are also important. Originally, the theoretical ideas were defined [2,3] in 1970-1971. By considering the contact of elastic bodies, it became evident that three parameters generally entered the equation for adhesive force F, as indicated below.

F = K [WEd3/(1-2)] 1/    (1)

where K was a constant, W the work of adhesion in Jm

-2, E the elastic modulus in Pa,  the Poisson’s ratio and d the dimension in metres. From this model, it is clear that the adhesion molecules have an effect on W, but elasticity E is equally influential and the geometry d is much more important. The most surprising thing about this new theory was that adhesion force was strongest when the surfaces were absolutely smooth and clean, with no projecting ‘lock and key’ and no adhesion molecules present.  In other words the effect of adhesion molecules was to reduce the adhesion force, not to cause it.

Umemori, H., The sticky synapse: Cell adhesion molecules, Springer Berlin 2009.
Kendall, K., The adhesion and surface energy of elastic solids, J PhysD: Appl Phys   4(1971) 1186-95.
Johnson, K.L.,  Kendall, K. and Roberts, A.D., Surface energy and the contact of elastic solids, Proc R Soc Lond  A324(1971) 301-313.

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Van der Waals adhesion supporting the gecko

Professor Kellar Autumn, Clark University, USA

Abstract

Geckos climb at speeds of over 1 m/s using adhesive nanostructures on their toes. Gecko toes bear angled arrays of branched, setae formed from stiff, hydrophobic beta-keratin that act as a soft bed of angled springs. Previously, we discovered that setae form a self-cleaning, anisotropic, mechanically switchable adhesive that adheres by van der Waals forces. Subsequently, we showed that humidity softens

and increases viscoelastic losses in setal keratin, increasing van der Waals adhesion. We employed the humidity effect on setal materials properties to test dynamic friction models for multicontact interfaces. Contact forces were materials-dependent domain at low velocity (< 1 mm/s) and materials-independent at higher velocity. This supports the rate-state model of sliding friction, in which shear force is the result of competition between rate-enhancing and contact-area-enhancing mechanisms. Natural and synthetic gecko setae can be employed as a model system in the study of interfacial forces. Smart materials properties of gecko-inspired adhesive nanostructures may enable rigid, inert, recyclable materials to replace glues, screws, and other attachment devices in the future.

References:

Puthoff, J, MJ Holbrook, M Wilkinson, K Jin, N Pesika, and K Autumn*. 2013. Dynamic friction in natural and synthetic gecko setal arrays. Soft Matter 9:4855-4863.

Puthoff J, M Prowse, M Wilkinson, & K Autumn*. 2010 Changes in materials properties explain the effects of humidity on gecko adhesion. J Exp Biol (213):3699-3704.

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Wet but not slippery: biomechanics of insect attachment organs

Dr Walter Federle, University of Cambridge, UK

Abstract

Adhesive pads of climbing animals provide interesting models for synthetic adhesives as they work under the most challenging conditions, including rough, wet or dirty substrates and extremely rapid attachment and detachment during locomotion. Adhesion is controlled dynamically via the directionality and shear force dependence of climbing pads. Insect adhesive organs make contact when pulled towards the body, and their adhesion increases linearly with pulling force, but they detach when pushed. Nevertheless, climbing insects can use their feet for pushing; they have evolved specialised "heel" pads for this purpose.

Although high friction is essential for insect adhesion, insects inject small volumes of fluid into the pad contact zone. In insects with smooth pads, this fluid is a water-in-oil emulsion which helps to reduce slipping. The secretion does not generally increase adhesion, but it helps to maximise contact area on rough substrates and allows insects to maintain strong adhesion during sliding. However, some specialised plant surfaces are lubricated and cause insects to slip.

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Session 2: Parameters controlling adhesion phenomena

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Chair - Dr Erich Sackmann

Physics of cell adhesion: biomimetic models- experimental tools- challenges

Professor Dr Erich Sackmann, Technische Universität München, Germany

Abstract

Cell-cell and cell-tissue adhesion are determined (i) by specific short range forces between cell surface proteins (CAMs), (ii) medium range interfacial forces mediated by Glycosurface charges and the Glycocalix (called repellers) and (iii) adhesion-induced elastic stresses in the composite elastic shell of cell envelopes. Basic physical concepts of cell adhesion revealed by experimental and theoretical studies of artificial and natural cells show:

  • Adhesion domains form  by clustering of CAMs (mediated by lateral phase separation) and are stabilized by coupling of CAM-clusters to the intracellular macromolecular network of the actin filaments and the aster-like assembly of microtubules.
  • Adhesion domains serve as force transmission centers between cells and tissue and act as  biochemical reaction centers mediating the generation of cell pushing forces by actin gelation. 

Adhesion domains enable cells to form strong adhesion domains by commitment of some 10,000 receptors. Together with the actin-microtubule crosstalk this enables cells to polarize and move by ongoing formation and dismantling of adhesion domains with a minimum of material turnover.  Cell polarization and locomotion can be understood in terms of a shell-string model of cells.

  

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Chair of session 2

Professor Dr Erich Sackmann, Technische Universität München, Germany

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Substrate elasticity dictates cell fate

Dr Florian Rehfeldt, Georg-August University Goettingen, Germany

Abstract

The mechanical properties of microenvironments in our body are very diverse and are as important to cells as biochemical cues. An especially striking experiment of this mechano-sensitivity demonstrated that the Young’s modulus E of the substrate directs the lineage differentiation of human mesenchymal stem cells (hMSCs).

I will show how a novel biomimetic ECM model based on hyaluronic acid (HA) that exhibits a widely tuneable and well-defined elasticity E, enables 2D and 3D cell culture to mimic a variety of distinct in vivo microenvironments. Quantitative analysis of the structure of acto-myosin fibres of hMSCs on elastic substrates, reveals that stress fibre morphology is an early morphological marker of mechano-guided differentiation. Furthermore, the cytoskeleton also dictates the shape of the nucleus and lends support to a direct mechanical matrix-myosin-nucleus pathway.

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Patterned surfaces, roughness and coating chemistry

Professor George Whitesides, Harvard University, USA

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Session 3: Parasites adhering to and entering cells

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Chair - Professor Gabriel Waksmann FRS

Biogenesis of adhesive pili at the outer membrane of bacterial pathogens

Professor Gabriel Waksman FRS

Abstract

Gram-negative pathogens commonly exhibit adhesive pili on their surface that mediate specific attachment to the host. A major class of pili is assembled via the chaperone/usher (CU) pathway. Type 1 and P pili have served as model systems for the elucidation of the CU biosynthetic pathway. Pilus assembly requires a periplasmic chaperone (FimC and PapD for type 1 and P pili, respectively) and an outer-membrane assembly platform termed “usher” (FiimD and PapC for type 1 and P pili, respectively). CU pilus subunits are produced in the cytoplasm, translocated to the periplasm by the Sec translocation machinery, and then taken up by a chaperone to cross the periplasmic space to reach the outer-membrane. At the outer-membrane, chaperone-subunit complexes are recruited to an outer-membrane assembly platform, the usher, which orchestrates recruitment and polymerization of subunits. Previous work has elucidated the molecular basis of chaperone function. Recent progress has shed light into the mechanism of pilus subunit assembly at the usher, leading to the elucidation of the entire cycle of pilus subunit incorporation.

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Attachment mechanisms in nature

Professor Stanislav Gorb, Kiel University, Germany

Abstract

The diversity of biological attachment structures is huge. By making a comparison of various attachment devices in biology we suggest that biological attachment systems can be subdivided into several groups according to the following principles: (i) fundamental physical mechanism, according to which the system operates, (ii) biological function of the attachment device, and (iii) duration of the contact. Eight fundamental attachment mechanisms have been previously recognized: (i) hooks, (ii) lock or snap, (iii) clamp, (iv) spacer or expansion anchor (v) suction, (vi) dry adhesion, (vii) wet adhesion (glue/cement, capillarity), and (viii) friction. Various combinations of these principles may also occur in real biological systems. From the biologists’ point of view, attachment devices may serve the following functions: (i) attachment of body parts to one another, (ii) attachment during copulation, (iii) phoresy or parasitism, (iv) dynamic attachment during locomotion, and (v) maintenance of position. According to the time scale of operation, different systems can be subdivided into three other groups: permanent adhesion, temporary adhesion and transitory adhesion. In this lecture, we discuss these classifications of biological attachment devices and draw some conclusions about the general relationships between the attachment mechanism and functional load of a biological attachment system. Finally, we show a biomimetic potential of studies of biological attachment devices.

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Malaria parasites adhering to red cells

Dr Pietro Cicuta, University of Cambridge, UK

Abstract

Erythrocyte invasion by Plasmodium falciparum merozoites has been  studied intensively, but our cellular understanding of invasion has been limited by the fact that invasion occurs very rapidly: it is generally  complete in within one minute, and shortly thereafter the merozoites, at least in in-vitro culture, lose their invasive capacity. The rapid nature of the process, and hence the narrow time window in which measurements can be taken, have limited the tools available to observe invasion. Here we employ optical tweezers to study individual invasion events for the first time, showing that newly released P. falciparum merozoites, delivered via optical tweezers to a target erythrocyte, retain their ability to invade. Even spent merozoites that had lost the ability to invade still retain the ability to adhere to erythrocytes, and also can still induce transient local membrane deformations in the erythrocyte membrane.  We use this technology to measure the strength of the adhesive force between merozoites and erythrocytes, and to probe the cellular mode of action of known invasion inhibitory treatments. These data have interesting implications for our current understanding of the cellular process of invasion, and demonstrate the power of optical tweezers technologies in unraveling  blood stage biology of malaria.

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Session 4: Viruses: contact and adhesion mechanisms

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Dr Michaela Kendall, University of Birmingham, UK

Process of nano-adhesion in the lung

Dr Michaela Kendall, University of Southampton, UK

Abstract

During inhalation, airborne nanoparticles steadily diffuse to, and deposit on, the lung surface.  The relatively sensitive, atmosphere exposed tissue of the lung has evolved to deal with nanoparticle exposure as a result.  The primary defence is not cellular, but opsonisation by protein and lipid covering the lung surface which aggregates material to increase recognition and removal by macrophage clean-up cells.  Proteomics of lung lining liquid shows how these protein components vary with individual, and even exposure history, thereby influencing the efficacy of this innate immune process that deals with both solid and biological nanoparticles e.g. combustion particles to viruses. Nano surface structure, plus adsorbed polymers, have long been known to influence the reception of material in the body, and new tools demonstrate nano-adhesive effects:  For example, surface adsorbed polymer attachment to porous surfaces dictate the success of surgical implant materials, and the presence of plasma polymers in serum prevents platelet activation by agonist nanoparticles.  In this session, we will compare viral/solid nanoparticle adhesion in biological systems, examine the role of adhesion in cell entry processes, and show how nanoparticle sequestration of polymers can affect virus infectivity.

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Structural investigation of calicivirus attachment - Ig-like cell adhesion molecules and virus entry

Dr David Bhella, University of Glasgow, UK

Abstract

As obligate intracellular parasites, viruses must traverse the host-cell plasma membrane to initiate infection. The first step in the viral entry pathway is engagement of a specific host macromolecule at the cell-surface. Several classes of molecule are exploited by diverse groups of viruses and many of these viral-receptors are involved in cell-adhesion. In particular immunoglobulin-like cell-adhesion molecules (IgSF CAMs) have been repeatedly identified as being critical for virus attachment and entry. One such example is Junctional Adhesion Molecule A, which is the receptor for Feline Calicivirus. Structure analysis of this virus-receptor complex provides valuable insights into the first stage of the infection process, identifying critical residues in both virus and receptor that are involved in attachment.  Furthermore interaction with the receptor induces structural changes in the viral capsid in preparation for genome release. Comparison of these data with structural studies of other Ig-CAM binding viruses does not shed light on why these molecules are so widely used. Moreover their use is surprising given the often occluded position of CAMs on the cell surface, for example at tight-junctions. Nonetheless the reason for their widespread involvement in virus entry probably originates in their functional rather than structural characteristics.

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Anti-viral adhesion molecular mechanisms

Professor Elspeth Garman, University of Oxford, UK

Abstract

Infection by the influenza virus depends firstly on cell adhesion via the sialic acid binding viral surface protein, haemagglutinin, and secondly on the successful escape of progeny viruses from the host cell to enable the disease to spread to other cells. To achieve the latter, influenza utilises another glycoprotein, the enzyme neuraminidase (NA), to cleave the sialic acid receptors from the surface of the original host cell. This talk will trace the development of anti-influenza drugs, from the initial suggestion by MacFarlane Burnet in 1948 that an effective “competitive poison” of the virus’ NA might be useful in controlling infection by the virus, through to the determination of the structure of NA by X-ray crystallography and the realisation of Burnet’s idea with the design of NA inhibitors. A focus will be the contribution of the late William Graeme Laver to this research.

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Session 5: Molecular modelling by computer and mechanics

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Professor Costantino Creton, ESPCI CNRS, France

Interface models

Professor Costantino Creton, ESPCI CNRS, France

Abstract

Interfaces play a major role in how objects and materials interact. This is even more true when the objects have specific molecules on the surface that can interact chemically such as in cells. However even for simple materials, modelling such interfaces with molecular detail is still a major challenge. Most molecular simulations packages represent reality at a certain length scale and with some level of detail. The greater the detail, the smaller is the volume that can be simulated. The process of simplification of the ingredients of the model to reach larger representative volumes is called coarse-graining and is well developed in the bulk, ie. for materials and fluids that have a homogeneous composition over the volume of interest. Interfaces pose a particular challenge because the composition, by definition changes spatially and the length scale over which this composition changes is generally poorly known. Several simulations methods have been developed by different communities based on their specific interest: Cohesive zone modelling in the solid mechanics community to transfer stresses1, 2, A thermodynamic approach to simulate equilibrium composition for physicists3, 4. Polymer deformation at interfaces (cohesive vs adhesive transitions)5, 6. Coarse-graining simulation of adhesion between latex particles with soft potentials7.

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Adhesion forces and protein structures

Dr Chin Yong, Science and Technology Facilities Council, UK

Abstract

We use molecular modelling techniques, namely the molecular dynamics (MD) simulations, to explore how polymer nanoparticles interact with the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid cell membranes. Two different polymers have been considered: polyethylene and polystyrene, both of which have wide industrial applications. We found that, despite the polar lipid headgroups can act as an effective barrier to prevent the nanoparticles from interacting with the membrane surface, irreversible adhesion can be initiated by insertion of dangling chain ends from the polymer into the hydrophobic interior of the membrane. In addition, alignment of chain segments from the polymers with that of hydrocarbon chains in the interior of the membrane facilitates the complete immersion of the nanoparticles into the cell membrane. These findings highlight the importance of the surface and the topological structures of the polymer particles that dictate the absorption behaviour on the membrane and, subsequently, induce the possible translocation into the cell.

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Genetic influence on contact structures

Professor Stephen Hart, University College London, UK

Abstract

Synthetic nanoparticles offer great promise in the development of nucleic acid-based therapies. Nanoparticles are self-assembling formulations, usually of cationic reagents, that package anionic nucleic acids and protect them from extracellular nucleases. In the transfection process, nanoparticles adhere to the target cell surface through receptors prior to endocytic uptake into the cell. Many different targeting ligands have been explored but we have developed short peptide ligands displayed on the surface of lipid-peptide nanocomplexes targeted to cell adhesion molecules such as integrins and ICAM-1. However, these, and most other self assembling nanoparticles, have a net positive charge on their surfaces, leading to non-specific binding, compromising cell specificity and in vivo biodistribution. Therefore we have developed anionic formulations  that display a much higher degree of targeting specificity, while maintaining efficiency of transfection. Anionic nanocomplexes achieved widespread dispersal in the brain from a single dose with effective transfected gene expression or RNAi.

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Session 6: Tracking nanoparticles to control adhesion

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Professor Terry Tetley, Imperial College London, UK

Nanoparticle toxicology

Professor Terry Tetley, Imperial College London, UK

Abstract

When nanosized material is inhaled a significant proportion can access the respiratory, alveolar region. Although the immune cells, (eg macrophages) and epithelium are the first cellular targets at this interface, the first biological membrane is the alveolar surfactant, a surface tension reducing material, rich in phospholipids and containing unique surfactant-associated protiens, SP-A, SP-B, SP-C and SP-D. This brief presentation will describe how the behaviour and toxicity of nanomaterials can be affected by their interaction with lung surfactant, an important biological membrane at the gas-liquid interface of the lung.

 

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Understanding the nano/bio interface for rational design of cancer nanotherapeutics

Professor Andre Nel, UC Center for the Environmental Impact of Nanotechnology, USA

Abstract

We have come to recognize that much of biology is executed at the nanoscale level, therefore providing a rational approach to using discovery about the structure and function of engineered nanomaterials (ENMs) at the nano/bio interface for interrogation of disease, diagnosis, treatment, and imaging at levels of sophistication not possible before.  Moreover, the behavior of ENM’s at the nano/bio interface also constitutes the basis for hazard generation and is important for understanding safety assessment and safer design of nanomaterials.  I will discuss how discovery at the molecular, cellular, organ and systemic nano/bio interfaces has assisted progress in development of nanocarriers.  I will explain how the physicochemical properties of nanomaterials relate to nanoscale interactions at the membrane, intracellular organelles, tissues and organs, allowing adaptation of nanocarriers to negotiate cellular and systemic barriers as well as safer design.  I will delineate how the use of high throughput screening to establish structure-activity relationships is used for design improvement of mesoporous silica nanoparticles to improve biodistribution and overcome the stroma of pancreatic cancer.

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N-cadherin antagonists as oncology therapeutics

Professor Orest Blaschuk, McGill University, Canada

Abstract

This presentation will focus on the cell adhesion molecule, known as N-Cadherin. Five topics will be discussed:

The mechanism by which N-cadherin promotes cell adhesion,

Role of N-cadherin in tumor blood vessels,

Participation of N-cadherin in cancer progression,

Development of N-cadherin antagonists, and

N-cadherin antagonists as anti-cancer drugs.

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Session 7: Chemical engineering of cells and applications

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Dr Liam Grover, University of Birmingham, UK

Utilising adhesion to shape engineered tissues

Professor Liam Grover, University of Birmingham, UK

Abstract

As the understanding of cell adhesion mechanisms improves, it is becoming possible to manipulate surface chemistry to initiate or prevent localised cell attachment.  This control over adhesion is being applied in a diverse range of research areas.  In regenerative medicine, for example, researchers are modifying material chemistry in order to prevent cell attachment and enable the expression of therapeutic factors or even to generate tissues ex-vivo by exploiting the natural ability of certain cell types to attach to or contract biologically derived matrices.   Such systems are also being used to evaluate systematically how spatial patterning of localised cell adhesion can modify biological response.  Avoiding cell adhesion is also important in many areas, and is being explored as a means to prevent fouling, either during industrial processing or plaque formation on the surface of enamel.  Within this session, the speakers will explore how the control and systematic evaluation of cell adhesion will have a broad impact in areas including chemical engineering process design, to the development of personal care products, through to the restoration of biological function.

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Advances in cell culture; anchorage dependence

Professor Otto-Wilhem Merten, Généthon, France

Abstract

Although for large scale manufacturing cells, such rCHO or recombinant myeloma cells, growing in suspension are preferred due to their advantageous technological features, anchorage dependent cells are still of high interest mainly for the following two purposes: i) production of viral vaccines at bioreactor scale using microcarriers, and ii) generation of cells at small scale for cell therapy purposes (amplification of stem cells). In both cases, the culture system has to provide sufficient culture surfaces for cell growth, which is, in particular, critical at a large scale using bioreactors due to the inherent hydrodynamic issues related to the use of microcarriers. This can be alleviated by novel cell culture devices at least a medium scale. Passaging/subcultivating adherent cells is a general issue because the cells have to be detached from their support for inoculating subcultures. This is traditionally performed using proteases (“trypsinisation”) despite many drawbacks. The talk presents an update on novel technological and biological ways to perform cultures of anchorage dependent cells and to replace cell detachment by less damaging and gentler ways to preserve the cells’ geno- and phenotypic features for their subsequent use.

   

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The association between dental biofilm and cancer

Dr Birgitta Söder, Karolinska Institutet, Sweden

Abstract

Dental plaque is a bacterial biofilm formed on dental surfaces. Dental plaque may also associate with systemic health and diseases due to hematogenic spread of oral microorganisms with subsequent up-regulation of cytokines and inflammatory mediators. For example, periodontitis is mediated by the inflammatory response to bacteria in the biofilm involving complex interactions with host defense.  Our hypothesis was that oral-dental infections associate with a number of life threatening diseases such as cancer.

We investigated the association between oral-dental infections with systemic health in a cohort follow-up since 1985. The aim was to compare baseline oral examination data with specific diagnoses from Swedish national cancer-, hospital- and death register databases. Our results confirmed the hypothesis by showing significant association between dental plaque and death in cancer (p<0.001)Thus, chronic oral diseases indeed seem to have detrimental health consequences probably by maintaining an often neglected systemic inflammatory burden.

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Session 8: Cancer cells and metastasis through low adhesion

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Professor Kevin Kendall FRS, University of Birmingham, UK

The next century prospect in cell adhesion

Professor Kevin Kendall FRS, Chemical Engineering, University of Birmingham, UK

Abstract

The purpose of this final session is to consider the wonderful advances in cell adhesion science that have been described at this discussion meeting, then to analyse where future progress might occur.  Harrison1 originally showed 100 years ago that animal cells required adhesion to a solid surface if they were to move, grow and reproduce. Following that invention of cultured cells, viruses could then be grown controllably within the cells so that the processes of virus attack and spread began to be understood. In a similar way, cultured cells have been exposed to nanoparticles in order to define how cell damage occurs. Further advances have been made in growing tissues and organs on special material substrates.How could this knowledge grow during the next century? First we review the questions about adhesion which have caused argument. Then follows a summary of the solutions to some of those controversies. Finally it is possible to speculate about potential advances and breakthroughs to come in future.Harrison,R.G., The reaction of embryonic cells to solid structures, J Expt Zool  17(1914)521-44.

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Cadherin molecules and bladder cancer

Dr Rik Bryan, University of Birmingham, UK

Abstract

Cadherins are the main mediators of cell-cell adhesion in epithelial tissues. E-cadherin is a known tumour suppressor and plays a central role in suppressing the invasive phenotype of cancer cells. However, the abnormal expression of other cadherins (“cadherin switching”) has been shown to promote a more invasive and malignant phenotype of cancer, with P-cadherin possibly acting as the principal mediator of invasion and metastasis in bladder cancer. Cadherins are also implicated in numerous signalling events related to embryonic development, tissue morphogenesis, and homeostasis. It is these wide-ranging effects and the serious implications of cadherin switching that make the cadherin cell adhesion molecules and their related pathways strong candidate targets for the inhibition of cancer progression, including bladder cancer. This lecture will focus on cadherin switching in the context of bladder cancer and will discuss other related molecules and phenomena, including EpCAM and the development of the cancer stem cell phenotype.

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Patterned surfaces, roughness and coating chemistry

Professor George Whitesides, Harvard University, USA

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Cell adhesion century: culture breakthrough The Royal Society, London 6-9 Carlton House Terrace London SW1Y 5AG UK