Modelling self-assembly and dynamics of biophysical & soft matter systems

本申请中提出的研究重点是控制“生物物质”和“生物材料”的物理和物理过程。目标是了解生命物质的基本物理过程，并将这些知识应用于基于聚合物、胶体和表面活性剂组装的新型功能软材料的设计。“生物物质”一词是指存在于生物物质中的分子、材料和结构，例如，脂质、蛋白质、膜和DNA，在它们的自然环境中。另一方面，“生物材料”是指使用有机/生物分子或结构作为构建块或其操作原理的人造或设计材料。

The research proposed in this application focuses on the physics and physical processes controlling 'biological matter' and 'biomaterials'. The goals are to understand the fundamental physical processes in living matter and to apply that knowledge to the design of new functional soft materials based on polymers, colloids and surfactant assemblies. The term 'biological matter' refers to molecules, materials and structures present in living matter, for example, lipids, proteins, membranes, and DNA, in their natural environment. 'Biomaterials', on the other hand, refers to man-made or designed materials that use organic/biological molecules or structures as building blocks, or for their principles of operation. The program I am proposing has two main themes: 1) Theoretical and computational modelling of cell division and migration and 2) multiscale modelling of the self-assembly of amyloid aggregation. Both themes focus on the physics of self-assembly and organization in complex biological and soft matter. As will be described, these two themes share several methodological connections and conceptually, they involve the physics of membrane interfaces at different levels of detail. Expertise in both themes is based on my previous research in modelling biological and soft matter systems. In cell division, the interactions between mechanical properties and biochemical regulation that are at the heart of cell division remain poorly understood. The fundamental importance of mechanical properties is easy to see: All cells, eukaryotic and prokaryotic, have a cytoskeleton. The cytoskeleton is a filament network consisting of a protein called actin as its main component, and is located on the cell membrane inside the cell. During cell division and cell motion, this network must change its properties – or even disintegrate locally and then re-assemble – in a controlled manner. In amyloid aggregation, on the other hand, membrane embedded misfolded proteins self-assemble, form pores and kill cells. We investigate the microscopic physical mechanisms that control self-aggregation. In the long term, such knowledge is crucial for opening new avenues of treatment. The methods we use are large-scale computational multi-scale modelling and analytical theory. Direct comparisons to experiments will be done with established collaborators. The problems described above define a Grand Challenge: 1) Finding the physical principles that drive and control self-assembly are crucial for understanding biological processes such as protein-protein interactions and formation of the toxic oligomeric assemblies that are characteristic in amyloid diseases. This knowledge is fundamental for bottom-up design of drugs and synthetic biological entities such as artificial cells. 2) Knowledge of the character and strength of the physical interactions together with collective properties in soft and biological matter is crucial for designing man-made materials that can be controlled by external stimuli such as mechanical forces or illumination by laser light. Applications include ultra-sensitive sensors for molecules, drug docking and designing new functional materials. In addition to new fundamental knowledge, this research will lead to method and software development (open source), benefiting the scientific community. My group has a very strong track record of contributing to and providing new simulation software and parameters for biophysical and soft matter systems. It is also anticipated that the results will spark experimental and applied research by other groups, and hopefully lead to consumer applications. Such developments would lead to added benefits for local and Canadian industrial R&D.