Molecular Dynamics modelling of Bone Tissue

在纳米尺度，即近分子水平，骨骼由位于胶原蛋白(即聚合物)基质中的微小矿物质组成。从宏观上看，骨骼的力学性能，尤其是骨骼的强度，会受到胶原蛋白、矿物质或胶原蛋白与矿物质相互作用的影响。导致分子结构变化从而最终导致骨折的条件包括：衰老、骨质疏松、儿童软骨病和成人软骨病、预防骨折药物的效果以及污染(众所周知铅在骨骼中积累)。这些情况给公共卫生系统带来了巨大的财政负担，并对个人造成了毁灭性的后果。实验技术的发展越来越多地允许描述骨骼分子尺度的结构变化，以及由于上述条件而导致的结构变化可以描述(尽管仍处于研究的前沿领域)。然而，这些结构变化对胶原蛋白和矿物质尺度上的力学(失效)的影响还知之甚少(因此，更大规模失效的根本原因也仍然知之甚少)。这一挑战的一个关键原因是，研究失效的传统工程方法是基于数百万分子的累积平均机械响应。为了了解骨骼分子尺度结构之间的力学行为，需要考虑在这个尺度上作用的分子作用力(静电相互作用)。分子动力学模拟提供了一种(现在已经相当成熟的)方法，它是研究这些基本问题的理想方法，但很少用于研究机械故障，更少用于研究骨的特性和导致其失效的机制的起源。本项目旨在开发一种基于分子动力学模型的严格方法，用于研究骨的纳米级力学行为。开发方法及其与组织宏观行为的联系将用于解决所提到的一种或几种情况(衰老、骨质疏松症等)。

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).