Large Scale Lattice Boltzmann for Biocolloidal Systems

Many of the most important structural components of biological materials exist on length scales of nanometres to microns. Examples include long polymers (such as DNA or flexible proteins), compact objects such as globular proteins (either in isolation or in structured assemblies such as the body of a virus); and lipid bilayer membranes (such as the walls that enclose the cells in our bodies). This range of length-scales is known as the colloidal domain. It is one where physical processes can be at least as important as biochemical ones; for instance, inside every cell, there are 'regulatory' proteins which have to search the genome (DNA) seeking preferential places of attachment (from which they then control the production of other proteins). To find these places, the regulatory proteins depend, at least in part, on the completely random motion, called Brownian motion, that occurs when particles on the colloidal scale are bombarded by the thermal energy of the surrounding solvent (water) molecules. This diffusive process is considerably complicated by the fact that motion of one colloidal object sets the surrounding solvent into motion, which causes all nearby objects also to move. This is referred to as a hydrodynamic interaction. Similarly, if one designs a drug delivery system in which drug molecules are encapsulated, the capsules are again on the colloidal scale but their motion in the bloodstream is dominated by their being swept along by the flow of blood, which is another form of hydrodynamic effect. In some modern therapies, magnetic colloids are steered with or against this flow by an external field; in such cases it is important to understand the effect of hydrodynamics on the response to a force.The physical consequences of hydrodynamic couplings in bio-colloidal systems are thus wide ranging. However, it is currently very difficult to predict any of these important effects, even using simplified models in which the biochemical detail of the colloidal objects is omitted. Fortunately, such problems can increasingly be addressed using very large scale computer simulation on some of the world's most powerful computers. The so-called lattice Boltzmann algorithm (LB) offers a specific technical solution to the challenges of hydrodynamics, by using a discrete lattice to model the flow of fluid from place to place. Unlike some other methods it can include the random forces responsible for Brownian motion. Also, as well as modelling colloids and polymers surrounded by simple solvents such as water, LB can also address solvents comprising complex fluids. The latter include the so-called 'amphiphilic mesophases' in which small molecules (with a water-loving head and water-hating tail) self-assemble into a labyrinth within which proteins or nanocolloids can reside. We aim to develop LB algorithms in the bio-colloidal context, and apply these to create new scientific knowledge that has been out of reach until now. Indeed we plan very large simulations of a range of hydrodynamic problems that lie at the interface between physics and the life sciences. These problems include: the flow of magnetic colloids in the blood stream as a model for 'Magnetic Drug Targetting' (MDT) on real patients; the motion of nanocolloids within amphiphilic mesophases suitable for drug delivery applications; the ejection of DNA from the body of a virus as it infects a cell; the dynamical behaviour of the highly confined DNA that is found within the bacterial and other cells; and the interaction between colloidal particles and DNA within the cellular environment. The last of these topics is crucial to understanding the problem of genome exploration by regulatory proteins as mentioned earlier, which we also plan to address. In all these areas, large-scale computer simulation has the potential to change the way science is done. We hope to establish a world lead for the UK in this emerging field.

The research planned in this proposal addresses areas where large, accurate simulation models can shed crucial light on the physical processes determining key aspects of biological function. Our adventurous scientific programme will have widespread benefits in pure and applied science, engineering, industry and health. Our proposed simulations on vascular flow and magnetic drug targetting (MDT) build directly on Coveney's GENIUS HemeLB project which involves clinical collaborators and the handling of patient-specific data on the layout of blood vessels. Development of patient-specific vascular simulation for MDT, if it can become part of established clinical practice, will be of obvious direct benefit to patients; it will also empower the clinicians who treat them, and potentially save costs by increasing success rates in complex treatment procedures. The work on colloidal transport in amphiphilic labyrinths will inform a wider body of ongoing research aimed at developing encapsulation technologies. Here the potential to benefit patients and their clinicians also exists in the longer term. The delivery systems modelled in this project may also have other commercially important applications, for instance in food technology and personal care products where controlled release of an encapsulated active agent is required. Our large scale simulations of DNA and biocolloid hydrodynamics in realistic geometries, including the interior of living cells, will be relevant to the many researchers now working at the physics / life sciences interface, including cell and bacterial biologists, biomedical engineers and possibly some clinicians. Although the majority of such researchers are academic, there are also quite large numbers in the commercial sector (particularly pharmaceuticals but increasingly also foodstuffs, remediation and biotech sectors). Alongside the biocolloidal applications that are the focus of this project, the lattice-Boltzmann simulation capability that we plan to develop could benefit a range of industrial sectors. For instance, recent Edinburgh codes, developed to address the design of new colloid-stabilized emulsion materials, were subsequently redeployed by researchers at Schlumberger to model multicomponent flows in porous media. Likewise UCL has ongoing collaborations, not only with the National Hospital for Neurology and Neurosurgery in haemodynamics simulation, but also with MI-SWACO in the area of optimising properties of drilling fluids for oil recovery. Thus our planned work on further developing lattice Boltzmann methods for colloids and polymers, as well as impacting scientifically on a wide range of stakeholders at the physics / life science interface through the specific scientific projects detailed in this proposal, has wider potential impact through development of new computational capabilities and software infrastructure. The latter is relevant to a broad class of colloidal and complex fluid materials used in industries such as chemicals, foodstuffs, personal care, and oil recovery.