Creating pattern from instability
The stability of colloids can also be dramatically altered by inclusion of polymeric materials. If the polymer interacts favourably with the particle surfaces, i.e. it 'adsorbs', then both an increase and a reduction in stability is possible, via modification of the electrostatic interaction of the polymer is charged or a reduction in the van der Waals attraction. The polymer layers, however, also introduces new contributions to the overall interaction between the particles. As two particles...
Adaptation experiments
The growth and development of organisms living within Earth's gravitational field are intricately linked to mechanical demands. Manipulation of forces in animal experiments has provided insights into the overall nature of the adaptation process. The characteristics of adaptation to increased or decreased in vivo loading include changes in bone quantity, not material quality greater response in immature than mature tissue and response to cyclic, not static, loading. These results were first...
Denis Noble
Denis Noble, 64, is the British Heart Foundation Burdon Sanderson Professor of Cardiovascular Physiology at the University of Oxford and a Fellow of Balliol College. In the early 1960s, he developed the first 'ionic' cell models of cardiac excitation and rhythm generation and has been at the forefront of computational biology ever since. As the Secretary-General of the International Union of Physiological Sciences, he has been pivotal to the initiation of a world-wide effort to describe human...
Paul W
School of Chemistry, University of Bristol, Bristol BS8 ITS, UK Diamond has some of the most extreme physical properties of any material, yet its practical use in science or engineering has been limited due its scarcity and expense. With the recent development of techniques for depositing thin films of diamond on a variety of substrate materials, we now have the ability to exploit these superlative properties in many new and exciting applications. In this paper, we shall explain the basic...
The chemistry of CVD diamond growth
The complex chemical and physical processes which occur during diamond CVD are comprised of a number of different but inter-related features, and are illustrated in Figure 5.3. At first sight, this may seem like a daunting array of physical and chemical reactions which need to be grasped if diamond CVD is to be understood. But over the past 10 years there have been a large number of studies of the gas phase chemistry, and we are now beginning to obtain a clearer picture of the important...
Simulating the ECG
To date, the most common tool for clinical assessment of cardiac electrical function is the electro-cardiogram (ECG). It is a dynamic representation, usually obtained from the body surface, of the changes in cardiac electrical behaviour. While the ECG is an invaluable tool for the observation of heart rate and rhythm, as well as for the diagnosis of conduction abnormalities, ischaemia, and infarcts, its detailed interpretation is not without pitfalls. One reason for this is that different...
Science or fiction
A patient who recently recovered from a minor heart attack is suffering from periods of ectopic ventricular beats, originating from what is believed to be a small area of post-ischaemic fibrosis in the free wall of the left ventricle. 1 This section will contain some of the more technical aspects of bio-mathematical modelling (in-depth information can be found in Kohl et al. 2000). The subsequent section on 'The utility of virtual organs' will address more general aspects that can be...
Visions of the Future Chemistry and Life Science
Leading young scientists, many holding prestigious Royal Society Research Fellowships, describe their research and give their visions of the future. The articles, which have been re-written in a popular and well-illustrated style, are derived from scholarly and authoritative papers published in a special Millennium Issue of the Royal Society's Philosophical Transactions (used by Newton this is the world's longest-running scientific journal). The topics, which were carefully selected by the...
The heart
Given that heart disease is the single largest cause of death in North America and Europe, finite-element models of the human heart have great potential clinical significance. The heart wall consists mostly of muscle, comprising millions of electrically activated contractile cells that are typically 0.1mm long and 0.015 mm wide. Note that the cell in Figure 9.2 is from the heart. Heart contraction is activated by an electrical impulse that is generated by cells in the heart's pacemaker. This...
Contributor biographies
Michael Thompson was born in Cottingham, Yorkshire, on 7 June 1937, studied at Cambridge, where he graduated with first class honours in Mechanical Sciences in 1958 and obtained his PhD in 1962 and his ScD in 1977. He was a Fulbright researcher in aeronautics at Stanford University and joined University College London (UCL) in 1964. He has published four books on instabilities, bifurcations, catastrophe theory and chaos and was appointed professor at UCL in 1977. Michael was elected a fellow of...
Peter Hunter
Peter Hunter, 52, is a NZ Royal Society James Cook Fellow and Chair of the Physiome Commission of the International Union of Physiological Sciences. He founded the Biomedical Engineering Group at Auckland University which, in close collaboration with the Auckland Physiology Department, uses a combination of mathematical modelling techniques and experimental measurements to reveal the relationship between the electrical, mechanical and biochemical properties of cardiac muscle cells and the...
Further reading
Dischler, B. & Wild, C. (eds.) 1998 Low-pressure synthetic diamond. Berlin Springer. This book goes into more detail about the technical aspects of making CVD diamond. May, P. W. 2000 Diamond thin films a 21st-century material. Phil. Trans. R. Soc. Lond. A, 358, 473-495. This gives a much more thorough and detailed scientific account of the subject. Spear, K. E. & Dismukes, J. P. 1994 Synthetic diamond emerging CVD science and technology. New York Wiley. This book gives a useful...
Preface
Writing here in a popular and well illustrated style, leading young scientists describe their research and give their visions of future developm ents. The book conveys the excitement and enthusiasm of the young authors. It offers definitive reviews for people with a general interest in the future directions of science, ranging from researchers to scientifically minded school children. All the contributions are popular presentations based on scholarly and authoritative papers that the authors...
The vision
The Physiome Project represents a world-wide effort to organise systematically the huge data mass on biological function into a 'quantitative description of the physiological dynamics and functional behaviour of the intact organism' (Bassingthwaighte). It was publicly initiated at the 33rd World Congress of the International Union of Physiological Sciences, 1997 in St. Petersburg (see http www.physiome.org). The Physiome Project sets a vision that will be much harder to accomplish than that of...
Info
Experimental and theoretical femtosecond spectroscopy of IBr dissociation. Experimental ionisation signals as a function of pump-probe time delay for different pump wavelengths given in (a) and (b) show how the time required for decay of the initally excited molecule varies dramatically according to the initial vibrational energy that is deposited in the molecule by the pump laser. The calculated ionisation trace shown in (c) mimics the experimental result shown in (b). recorded as...
Visions for the future
With these new tools and so many unanswered questions about tissue function and maintenance, the time for mechanobiology has truly arrived. High-resolution imaging systems will allow us to determine tissue structures from the highest hierarchy of the organ to the lowest of the genome. These digital images are ideally suited for analysing physical forces and linking continuum level tissue stresses to deformation-induced gene activation in the DNA molecule. Advances in dynamic systems theory and...
The inertia of natural patterns
In his inspiring work On growth and form, D'Arcy Thompson saw that the production of many relatively small scale biological structures such as radiolarian skeletons and the spiral shells of many marine organisms resulted from packing phenomena (as in pine cones or sunflowers) upon surfaces or in three dimensions. Today his work is perhaps seen as being overly directed to the description of nature by 'natural' mathematical rules, very much in the Greek tradition. However, the nub of his argument...
D J Macquarrie
Born in Oban, Argyll, in 1960, Duncan Macquarrie studied Pure and Applied Chemistry at the University of Strathclyde, graduating with a first class degree in 1982 and a PhD in 1985. He then moved to York, where he carried out research in Phase Transfer Catalysis. He subsequently spent time in industry, where he worked in the UK and abroad, mostly in synthetic chemistry, but always with an interest in method development and catalysis. He returned to York in 1995 to take up a Royal Society...
An ear model
Whilst finite-element modelling of gap junctions occurs at a sub-cellular level, these models do not consider the operation of intact organs. Conversely, in models of the complete heart the discretisation is usually on a millimetre scale. However, the cochlea (see Figure 9.3) is already being simulated on a 0.01mm, or cellular, scale. Although cochlear malfunction is not life threatening, damage to it does adversely affect the ability of almost 1000000000 people to communicate. Figure 9.4. (a)...
J M Goodman
Jonathan Goodman studied chemistry at Cambridge, graduating with a BA in 1986, and with a PhD in organic chemistry in 1990. He then worked at Columbia University, New York, with Professor Clark Still, before returning to Cambridge as a Research Fellow at Clare College. He is now a Royal Society University Research Fellow in the Department of Chemistry, and uses both computational and experimental techniques to study organic chemistry. He is aged 35, and has recently published a book with the...
Bone growth and maintenance
Bone forms through two different developmental processes endochondral ossification and intramembranous ossification. Endochondral ossification involves an intermediate tissue stage, cartilage, not present in intramem-branous formation. The long bones all form endochondrally. In these bones, development begins with the condensation of mesenchymal cells, which differentiate into chondrocytes (Figure 7.3), creating a cartilage pre-pattern of the skeleton. The first bony tissue, known as the bone...
Summary The virtual heart
Analytical models of the heart are a reality. They are based on detailed descriptions of cardiac tissue architecture and anatomy, including the coronary vasculature. In silico cardiac tissues possess realistic passive mechanical properties, and both electrical and mechanical activity can be simulated with high accuracy. Descriptions of key components of cellular metabolism have been introduced, as have models of drug-receptor interactions. The individual modules of the in situ heart can be...
Green chemistry
The chemical industry today is one of the most important manufacturing industries in the world. The ability of chemists to produce a wide range of different molecules, both simple and staggeringly complex, is very well developed, and nowadays almost anything can be prepared, albeit maybe only on a small scale. On an industrial scale, a great variety of products are synthesised, using chemistry which varies from simple to complex. These products go into almost all the consumer goods we take for...
Contents
Thompson page vii 1 Laser snapshots of molecular motions 1 2 Enzymology takes a quantum leap forward 21 Michael J. Sutcliffe and Nigel S. Scrutton 3 World champion chemists people versus computers 43 Jonathan M. Goodman 4 Chemistry on the inside green chemistry in mesoporous materials 59 5 Diamond thin films a twenty-first century material 75 6 The secret of Nature's microscopic patterns 95 Alan R. Hemsley and Peter C. Griffiths 7 Skeletal structure synthesis of mechanics...
Cell interactions
Of growing interest world-wide is the possible carcinogenic effect of low-frequency non-ionising electromagnetic radiation, such as that emitted from power lines. Possible candidates for explaining sensitivity to electromagnetic fields are the gap junctions that exist between cells in many types of tissue. These junctions are similar to the protein-based channels that enable ions to pass across cell membranes, except that they span the extracellular space between adjacent cells. Gap junctions...
Modelling
For a skeletal element to respond to its mechanical environment, the cells in the tissue must regulate their environment in response to the mechanical stimuli they receive. The regulatory process can be thought of as a feedback loop (Figure 7.5) in which the osteocyte senses the stimulus and Figure 7.5. Feedback diagram for skeletal mechanical regulation. When forces are applied to a whole bone, the stimulus that results is sensed by the bone cells in the tissue. The sensor cells then signal...
The unexpected behaviour of tiny objects
Whilst our understanding of the relevant factors important to colloid science in terms of synthetic applications and materials (e.g. paints) is quite advanced, as we have seen the same cannot be said for the 'colloid science' operating in natural environments. This is surprising since many of the same types of materials are present in the natural environment, e.g. spherical particles comprising silica or a monomer, free polymer, salt and other additives such as fatty acids. Furthermore, the...
The substrate material
Most of the CVD diamond films reported to date have been grown on single crystal silicon wafers, mainly due to its availability, low cost, and favourable properties. However, this is by no means the only possible substrate material - although any candidates for diamond growth must satisfy a number of important criteria. One requirement is obvious - the substrate must have a melting point higher than the temperature required for diamond growth (normally > 700 C). This precludes the use of...
Walsh
Algorithm, genetic, 56 animal electricity, 171 antichaos, 100 applications of diamond films, 88 Astronomy and Earth Science, companion book, preface atom-laser interactions, 2-3 atom-molecule collisions, ultrafast dynamics of, 11-14 atomic motions, optical control over, bicontinuous mixtures, 98 bone adaptation computer simulation of, 121 experiments, 119 bone and skin, mechanics of, 157 bone cells and matrix, 116 bone growth and maintenance, 118 brain, 171 damage, 175, 178 electrical...
Applications
The initial applications of MTSs were, perhaps not surprisingly, simply attempts to reproduce zeolite chemistry on larger molecules. This chemistry is based on the fact that the aluminium centres in zeolites cause a negative charge to exist on the framework of the solid this charge must be balanced by a cation. When the cation is a hydrogen ion (proton), the material is an acid, and indeed some zeolites are very strong acids indeed. However, the acidity of the corresponding MTSs is much lower,...
Carriers
Scheme of a ventricular action potential (a) and its sub-cellular mechanisms (b). Membrane potential models simulate action potentials (a) with a deliberately small number of equations ionic current models reproduce the action potential on the basis of calculating the sub-cellular ion movements that actually give rise to it (b). (a) Cardiac contraction is controlled by an electrical waveform called action potential. Action potentials are induced by change in cell voltage to less...
Particle detectors
One area where CVD diamond is beginning to find a market is as a detector for ultraviolet light and high energy particles. High performance ultraviolet detectors have already been demonstrated and are now in commercial production. Diamond can be used to detect other high energy particles (such as alpha- and beta-particles and neutrons), and be used as a replacement for silicon in the next generation of particle accelerators. Since diamond has a similar response to damage by X-rays and gamma...
I
All skeletal tissues arise from a single cell type, the mesenchymal stem cell. Differentiation into bone, cartilage, muscle, or ligament occurs in response to the mechanical and biochemical stimuli of the stem cell's environment. osteoblasts. Upon activation, osteoblasts secrete osteoid, the organic extracellular matrix into which mineral crystals are deposited. The organic matrix contains 90 per cent collagen and a ground substance consisting of large protein polysaccharides and a...
Future prospects
The chemical industry produces an enormous range of products, from petrol and other fuels, to additives which improve the performance of the fuels, to plastics and fabrics (including the colours and fire retardants which make them attractive and safe), colours, flavours and fragrances, and further to the most complex molecules, which find use as agrochemicals and pharmaceuticals. One of the strongest current trends in the industry is towards green chemistry, which will involve redisign of many...
Organ models
Clearly, cardiac function may not be addressed exclusively on the basis of describing the working mechanisms of single cells. Both normal and disturbed heart rhythms are based on a spreading wave of electrical excitation, the meaningful investigation of which requires conduction pathways of at least hundreds if not thousands of cells in length. These may be produced by grouping together multiple cell models to form virtual tissue segments, or even the whole organ. The validity of such...
Added value for drug and device development
Drug development is currently largely based on trial and error. This is an exceedingly time-consuming process, and some of the associated errors have proved quite costly for patients involved. Even if distressing consequences of clinical testing could be avoided, the economical costs of bringing a new drug to market are prohibitive close to US 0.5 billion. Also, the fact that only an estimated 10 per cent of pre-clinically tested lead-compounds are likely to ever reach the market must...
Martians and the Highway Code
From Mars, to keep things simple. You are given the assignment, should you accept it, to report on the use of cars by humans. Please read on - this book will not self-destruct in a few seconds . . You could visit earth, hire a mechanical workshop in a remote area, car-jack a few specimens, and dissect them. You would observe that cars differ in their colour, shape, size and spec. Some may even contain a bar, cinema or swimming pool, but, perhaps, limousines are...
Introduction
Your body is an extraordinarily complex piece of biological machinery. Even when you are sitting still in a quiet room your blood is being pumped to every tissue, your kidneys are filtering body fluids, your immune system is guarding against infection and your senses are continuously monitoring all kinds of information from their surroundings. Scientists are very good at studying single molecules and single cells but the challenge of understanding molecular and cellular processes in entire...
Imaging
A key new tool in the validation of analytical models is high-resolution imaging coupled with computer analyses to calculate the material stresses, strains, and stimuli within cancellous bone. The average thickness of a trabecula is 100-150 m, undetectable with conventional computed tomography resolution of 100-200 m. Microcomputed tomography can image bone at 17 m resolution, and the images can be converted directly into large-scale finite element models (Figure 7.7). These models can...
Composite reinforcement
Diamond fibres and wires have been fabricated (see Figure 5.7), which show exceptional stiffness for their weight. If growth rates can be increased to economically viable levels, such diamond fibres may find uses as reinforcing agents in advanced composites, allowing stronger, stiffer and lighter load-bearing structures to be manufactured for use in, say, aerospace applications. Hollow diamond fibres and two-dimensional diamond fibre mat- Figure 5.7. A diamond-coated tungsten wire that is about...
Marjolein C H van der Meulen
Born in 1965 in Utrecht, the Netherlands, Marjolein van der Meulen received her Bachelors' degree in mechanical engineering from the Massachusetts Institute of Technology in 1987. Thereafter, she received her MS (1989) and PhD (1993) from Stanford University. She spent three years as a biomedical engineer at the Rehabilitation R& D Center of the Department of Veterans Affairs in Palo Alto, CA. In 1996, Marjolein joined the faculty of Cornell University as an Assistant Professor in the Sibley...
Future applications of biocolloid selfassembly
Clearly the improved understanding of colloidal behaviour within living systems that we are developing offers the eventual prospect of our being able to manipulate such systems. The control of microarchitecture in both living and synthetic systems has many potential applications. The most important aspect is the ability to define the particular conditions under which a certain pattern or structure will be formed such that the products will be uniform. This clearly happens in Nature, but natural...
The biology of microarchitecture and selfassembly 611 Message and machinery
Man-made structures and architecture operate under similar constraints. Three factors come together to produce the final object. There is a design in the form of a blueprint, the workforce to manipulate the components, and the components themselves whose physical properties also play a role in determining the ultimate form. One cannot build a car engine from rubber or Wellington boots from steel. Classical Greek architecture Figure 6.1. All scales refer to bar in (b). (a) The silica frustule...
The next 10 years
We are at the threshold of a new era in biological research. Finite-element computer models are transforming our understanding of complete organs. Some organs, such as the cochlea, are already being modelled at a cellular level. Other organs, such as the heart, are represented by models that are more structurally accurate, and they incorporate interactions between different forms of energy. These different strategies for balancing structural realism against spatial resolution will continue to...
The year 2020
It is difficult to predict developments beyond the first decade of the twenty-first century. However, there are two arenas in which modelling and biology may converge even further, namely developmental biology and carbon-based computing. Developmental biology is an area of experimental research that is expanding rapidly. Current tissue-based work on coch-lear regeneration highlights the difficulties of artificially controlling the Figure 9.7. The amplitude of the basilar membrane displacement...
Mimicking and modelling nature
The production of artificial microscopic structures with similar architecture to that produced by microorganisms has been pioneered by Stephen Mann. As in our experiments (below), the production of microstructure Figure 6.2. (a). Colloidal silica network on the surface of spores from Isoetes pantii (quill wort). Scale 20 m. (b). Polystyrene networks and foams produced as a biproduct of colloidal latex formation. Both types of colloidal system are typical of the diversity of patterns that can be...
O
Possibilities for the synthesis of Vitamin K3. The small pore titanium zeolite TS-1 cannot fit the large naphthalene molecule into its pore system, and thus is effective in this transformation. The larger titanium MTS material is capable of interacting with the molecule, and the desired transformation can take place. taining materials have been prepared by three different routes. These materials are capable of the fast and efficient catalysis of several reactions with excellent...
Bone structure
The geometry and structure of a bone consist of a mineralised tissue populated with cells. This bone tissue has two distinct structural forms dense cortical and lattice-like cancellous bone, see Figure 7.2(a). Cortical bone is a nearly transversely isotropic material, made up of osteons, longitudinal cylinders of bone centred around blood vessels. Cancellous bone is an orthotropic material, with a porous architecture formed by individual struts or trabeculae. This high surface area structure...
Methods for production of CVD diamond
All CVD techniques for producing diamond films require a means of 'activating' gas phase carbon-containing precursor molecules. This activation can involve heating (e.g. a hot filament), or an electric discharge, such as a plasma. Figure 5.2 illustrates two of the more popular experimental methods. While each method differs in detail, they all share a number of features in common. For example, growth of diamond (rather than graphite) normally requires that the precursor gas (usually methane,...
Jonathan M Goodman
Department of Chemistry, Cambridge University, Lens, CB2 1EW, UK Making molecules has been important to human society from prehistoric times. The extraction of tin and lead from their ores has been possible for thousands of years. Fermentation has also been controlled to produce alcohol for millennia. In the past century, carbon-containing molecules have become increasingly important for the development of new substances, including plastics, other new materials and health products. Organic...
Of patterns and species
Differences in microarchitecture in relation to component concentration would appear to occur in our simulations of Selaginella megaspore wall construction. Imagine an example in which our synthetic wall structure is determined by concentration of styrene and cyclohexane (in the plant, these would be sporopollenin monomer and a fatty acid) all in water. Different arrangements (and sizes) of polystyrene particles occur depending upon the conditions at the initiation of polymerisation. In the...
