Molecular Dynamics modelling of Bone Tissue

在纳米级，即接近分子水平，骨由位于胶原蛋白基质（即聚合物）内的微小矿物血小板组成。骨的宏观力学性质，特别是骨的强度，受到胶原蛋白、矿物质或胶原蛋白与矿物质之间相互作用的影响。导致分子尺度结构变化并最终导致骨折的条件包括：老龄化、骨质疏松症、儿童佝偻病和成人骨软化症、预防骨折药物的影响以及污染（已知铅会在骨骼中积累）。这些疾病给公共卫生系统带来了巨大的财政负担，给个人带来了毁灭性的后果。实验技术的发展越来越多地允许在分子尺度上描述骨的结构变化，并且可以描述由于上述条件引起的结构变化（尽管仍然是研究的前沿领域）。然而，这些结构变化对胶原蛋白和矿物质规模的力学（失效）的影响知之甚少（因此，更大规模失效的根本原因也知之甚少）。这一挑战的一个关键原因是，传统的工程方法研究故障是基于数百万分子的累积平均机械响应。为了理解骨的分子尺度结构之间的力学行为，需要考虑在该尺度下作用的分子力（静电相互作用）。分子动力学模拟提供了一个（现在已经相当发达）的方法，这是理想的放置，以研究这些基本问题，但很少用于调查的目的，机械故障，更很少用于调查的骨性能和其失败的机制的起源。本项目旨在开发一个严格的方法，基于分子动力学建模的目的，研究骨纳米，规模机械性能。开发方法及其与组织宏观行为的联系将用于解决一种或几种提到的情况（老化、骨质疏松等）。

At the nano-scale, i.e. near molecular level, bone consist of tiny mineral platelets located within a matrix of collagen (i.e. a polymer). The mechanical properties of bones as perceived at the macroscale, notably the strength of bone, is affected by changes in the collagen, the mineral or the interaction between the collagen and the mineral. Conditions that cause changes in molecular scale structures and thus ultimately bone fractures include: ageing, osteoporosis, rickets in children and osteomalacia in adults, effect of fracture preventive drugs as well as pollution (lead is known to accumulate in bone). These conditions present a huge financial burden on public health systems and devastating consequences for individuals. Developments in experimental techniques are increasingly allowing a description of the structural changes at the molecular scale of bone and the structural changes due to the conditions mentioned above can be described (although still a field at the forefront of research). However, the effect of these structural changes on the mechanics (failure) at the scale of the collagen and mineral is poorly understood (and thus the fundamental causes of failure at a larger scale also remains poorly understood). A key reason for the challenge is that traditional engineering methods investigating failure are based on the accumulated average mechanical response of millions of molecules. To understand the mechanical behaviour between the molecular scale structures of bone, the molecular forces (electrostatic interactions) acting at this scale need to be considered. Molecular dynamics simulations provide a (now reasonably well-developed) method, which is ideally placed to investigate these fundamental issues but are rarely used for the purposes of investigating mechanical failure and even more rarely for investigations of bone properties and the origins of the mechanisms governing their failure.This project aims to develop a rigorous method based on molecular dynamics modelling for the purposes of investigating bone nano-scale mechanical behaviour. The develop method, and its link to the macroscopic behaviour of the tissue, will be used to address one or several of the mentioned conditions (ageing, osteoporosis etc).