Molecular Dynamics modelling of Bone Tissue

骨组织的分子动力学建模

• 批准号: 2738529
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2738529
• 关键词: Molecular; Dynamics; modelling; Bone; Tissue

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).

在纳米尺度上，即接近分子水平，骨骼由位于胶原蛋白基质（即聚合物）内的微小矿物质血小板组成。在宏观尺度上，骨骼的力学特性，特别是骨骼的强度，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变化的影响。导致分子尺度结构改变并最终导致骨折的条件包括：衰老、骨质疏松、儿童佝偻病和成人骨软化症、预防骨折药物的作用以及污染（已知铅会在骨骼中积聚）。这些疾病给公共卫生系统带来了巨大的财政负担，并给个人带来了毁灭性的后果。实验技术的发展越来越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的力学（失效）的影响知之甚少（因此，在更大范围内失效的根本原因也知之甚少）。这一挑战的一个关键原因是，传统的工程方法是基于数百万个分子累积的平均机械响应来研究故障的。为了理解骨的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力（静电相互作用）。分子动力学模拟提供了一种（现在相当发达的）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的目的，更很少用于研究骨特性和控制其故障机制的起源。本项目旨在开发一种基于分子动力学建模的严谨方法，用于研究骨纳米级力学行为。开发方法及其与组织宏观行为的联系将用于解决上述一种或几种情况（衰老，骨质疏松症等）。