Cell biomechanics and its applications in human disease diagnosis

Certain diseases are known to cause changes in the physical and biomechanical properties of cells.These include cancer,malaria,and sickle cell anemia among others.Typically,such physical property changes can result in several fold increases or decreases in cell stiffness,which are significant and can result in severe pathology and eventual catastrophic breakdown of the bodily functions.While there are developed biochemical and biological assays to detect the onset or presence of diseases,there is always a need to develop more rapid,precise,and sensitive methods to detect and diagnose diseases.Biomechanical property changes can play a significant role in this regard.As such,research into disease biomechanics can not only give us an in-depth knowledge of the mechanisms underlying disease progression,but can also serve as a powerful tool for detection and diagnosis.This article provides some insights into opportunities for how significant changes in cellular mechanical properties during onset or progression of a disease can be utilized as useful means for detection and diagnosis.We will also showcase several technologies that have already been developed to perform such detection and diagnosis.     

On the relationship between the dynamic behavior and nanoscale staggered structure of the bone

Bone, a typical load-bearing biological material, composed of ordinary base materials such as organic protein and inorganic mineral arranged in a hierarchical architecture, exhibits extraordinary mechanical properties. Up to now, most of previous studies focused on its mechanical properties under static loading. However, failure of the bone occurs often under dynamic loading. An interesting question is: Are the structural sizes and layouts of the bone related or even adapted to the functionalities demanded by its dynamic performance? In the present work, systematic finite element analysis was performed on the dynamic response of nanoscale bone structures under dynamic loading. It was found that for a fixed mineral volume fraction and unit cell area, there exists a nanoscale staggered structure at some specific feature size and layout which exhibits the fastest attenuation of stress waves. Remarkably, these specific feature sizes and layouts are in excellent agreement with those experimentally observed in the bone at the same scale, indicating that the structural size and layout of the bone at the nanoscale are evolutionarily adapted to its dynamic behavior. The present work points out the importance of dynamic effect on the biological evolution of load-bearing biological materials.     

微流控通道内细胞及其初级纤毛的力传导行为

细胞处于复杂的生理环境之下,附着在细胞表面的初级纤毛被认为是重要的力学信号传感器,其与细胞的代谢、发育、分裂和增殖等生理活动密切相关.为了研究细胞及其初级纤毛在微流体环境下的力传导行为,本文建立了力-电协同驱动下的矩形微流控通道和含有多孔黏弹性属性的贴壁细胞有限元模型系统.考察了细胞的细胞质和细胞核在振荡层流下的应力、应变、孔隙压力和孔隙流速等力学信号响应,量化研究了初级纤毛作为细胞独特的力学感受器的生物力学行为. 结果表明:细胞在振荡层流下的力学响应表现出和外加力-电驱动载荷相同的震荡规律.渗透率是细胞多孔弹性力学行为的主要影响因素. 初级纤毛是细胞主要的力学感受器,细胞可以通过纤毛长度和直径调节其力学感受敏感性(应力影响区域),随着初级纤毛长度的增大, 其纤毛挠曲刚度减小, 但是敏感性增大.模型的建立为进一步研究微流体剪切作用下的细胞生长、分化等微观机理提供基础,同时也为检测细胞微结构器(纤毛等蛋白链)的力学性能提供了理论技术支持.      

MECHANOTRANSDUCTION OF THE CELL AND ITS PRIMARY CILIUM IN THE MICROFLUIDIC CHANNEL 1)

细胞处于复杂的生理环境之下,附着在细胞表面的初级纤毛被认为是重要的力学信号传感器,其与细胞的代谢、发育、分裂和增殖等生理活动密切相关.为了研究细胞及其初级纤毛在微流体环境下的力传导行为,本文建立了力-电协同驱动下的矩形微流控通道和含有多孔黏弹性属性的贴壁细胞有限元模型系统.考察了细胞的细胞质和细胞核在振荡层流下的应力、应变、孔隙压力和孔隙流速等力学信号响应,量化研究了初级纤毛作为细胞独特的力学感受器的生物力学行为. 结果表明:细胞在振荡层流下的力学响应表现出和外加力-电驱动载荷相同的震荡规律.渗透率是细胞多孔弹性力学行为的主要影响因素. 初级纤毛是细胞主要的力学感受器,细胞可以通过纤毛长度和直径调节其力学感受敏感性(应力影响区域),随着初级纤毛长度的增大, 其纤毛挠曲刚度减小, 但是敏感性增大.模型的建立为进一步研究微流体剪切作用下的细胞生长、分化等微观机理提供基础,同时也为检测细胞微结构器(纤毛等蛋白链)的力学性能提供了理论技术支持.     

CD44-配体相互作用的生物力学与功能调控

作为一种广谱表达的细胞粘附分子, I型跨膜糖蛋白CD44(cluster of differentiation 44)参与细胞增殖、分化、迁移, 血管生成等生物学过程,对于介导细胞信号转导, 调节组织稳态等功能具有关键作用. 特别地,CD44-选择素、CD44 -透明质酸相互作用介导的细胞粘附动力学在经典炎症反应、肿瘤转移或组织特异的肝脏免疫中具有重要作用.该综述分别从细胞层次粘附动力学、二维与三维条件下的分子层次反应动力学、原子层次微观结构以及胞内信号转导通路等方面综述了CD44 -选择素、CD44 -透明质酸相互作用的研究进展及尚待回答的生物力学问题.力学、物理因素对生命活动的不可或缺性逐渐被研究者们接受,力学医学、力学免疫学、力学组学等新概念相继提出. 生理、病理条件下,CD44 -配体相互作用介导的细胞粘附必将受到血流剪切、基底硬度等力学、物理微环境的调控,但是其调控机制还远不清楚. 基于此,本文就CD44 -配体相互作用相关的未来研究方向做出展望, 主要包括:力学、物理因素如何调控CD44 -配体相互作用介导的细胞粘附动力学及其内在机制;CD44 -配体相互作用反应动力学的力学调控规律及结构基础是什么;以及力学作用下CD44 -配体相互作用原子层次的微观结构如何发生动态演化.本文可为深入理解CD44 -配体相互作用的生物学功能及其结构功能关系提供线索.      

Mechanical Properties of two novel planar lattice structures

Two novel statically indeterminate planar lattice materials are designed: a new Kagome cell (N-Kagome) and a statically indeterminate square cell (SI-square). Their in-plane mechanical properties, such as stiffness, yielding, buckling and collapse mechanisms are investigated by analytical methods. The analytical stiffness is also verified by means of finite element (FE) simulations. In the case of uniaxial loading, effective modulus, yield strength, buckling strength and critical relative density are compared for various lattice structures. At a critical relative density, the collapse mode will change from buckling to yielding. Elastic buckling under macroscopic shear loading is found to have significant influence on failure of lattice structures, especially at low relative densities. Comparison of the analytical bulk and shear moduli with the Hashin–Shtrikman bounds indicates that the mechanical properties of the SI-square honeycomb are relatively close to being optimal. It is found that compared with the other existing stretching-dominated 2D lattice structures, the N-Kagome cell possesses the largest continuous cavities for fixed relative densities and wall thicknesses, which is convenient for oil storage, disposal of heat exchanger, battery deploying and for other functions. And the initial yield strength of the N-Kagome cell is slightly lower than that of the Kagome cell. The SI-square cell has similar high stiffness and strength as the mixed cell while its buckling resistance is about twice than that of the mixed cell.     

力敏感受体介导细胞功能调控的力学生物学研究

细胞膜是细胞与外部环境进行物质与能量交换的界面,是调节细胞正常生命活动的重要结构基础.细胞膜上力敏感受体可通过力学作用方式参与并影响细胞的力信号转导等功能.整合素和钙黏素是细胞膜上典型的力敏感受体,可介导细胞与细胞周围基质或邻近细胞发生力学作用,并将力学刺激信号转导为生化信号,进而激活细胞内一系列应答反应,最终影响细胞生长、分化、增殖、凋亡和迁移等功能.力敏感受体介导细胞功能调控研究已成为探索细胞主动响应外界复杂力学微环境的力学生物学机制的关键,为进一步深入认识生理和病理状态下细胞功能变化规律,为揭示疾病的发生、发展机制提供重要的力学生物学理论与实验依据.本文总结了力敏感受体介导细胞功能调控的国内外研究进展;介绍了黏附界面处典型力敏感受体的结构和功能;总结了这些力敏感受体参与的细胞力信号感知与响应的数理模型;概述了细胞通过力敏感受体进行力学信号转导的过程;介绍了黏附介导细胞功能调控的力学生物学过程和机制;简述了体外构建模拟细胞力学微环境中细胞-细胞外基质和细胞-细胞力学相互作用的技术;指出了力敏感受体介导细胞功能调控的力学生物学研究发展趋势和未来方向.     

折纸超材料折展稳态特性研究

Origami metamaterials can regulate and control macroscopic deformation by continuous deformation of their internal microstructure. Hence, mechanical properties such as Poisson's ratio, stiffness, and modulus of the metamaterials can be adjusted and designed. This work theoretically studied the mechanical behavior of origami metamaterials under the synergy of complex internal configuration and folding motion, with the methods of torsion spring equivalent and energy principle. Here, we established a mechanical model to describe the folding deformation of the metamaterials, and analyzed the influence of geometric parameters on external loading. Through parameter analysis, it is found that the external loading exhibits monotonicity during the unfolding process and does not have stability. The external loading can show three situations such as monotonicity, mono-stability and bi-stability during the folding process, which are closely related to the parameters. This work provides important guidance to origami metamaterials for improving the design of the configuration and the regulation of their performance.      

The Effect of Strain Rate,Specimen Geometry and Lubrication on Responses of Aluminium AA2024 in Uniaxial Compression Experiments

The ability to observe and quantify intrinsic material response to loading at different rates of strain has been improved by reducing the errors of mechanical characterisation in uniaxial compression experiments. In order to perform comparisons of the results from uniaxial compression tests used to characterise mechanical properties of aluminium alloys at different strain rates, it is necessary to reduce errors resulting from factors such as specimen design. In this study, the effects of strain rate, specimen geometry and lubrication on the compressive properties of aluminium AA2024 alloy were quantitatively investigated by measuring the mechanical behaviour of this alloy as functions of strain rate, specimen aspect ratio and lubrication condition. Both the deformation history and the failure mode were identified using low and ultrahigh speed photography. The interaction of factors influencing the measured stress-strain response was quantified, and suitable specimen aspect ratios for compression tests at different strain rates were identified.     

细胞铺展动力学的研究进展

细胞与细胞外基质之间的相互作用在细胞的迁移、分化、凋亡等生理过程中起着重要的作用,细胞铺展作为细胞与细胞外基质作用的第1步,受到了人们的广泛关注.首先阐述了细胞铺展的关键生物动力学过程,对铺展3个不同阶段的特点进行了总结和归纳,并运用力学的观点阐明了细胞铺展的驱动力及驱动机制,详细讨论了聚合力、黏附力以及细胞张力等3种主要作用力在细胞铺展过程中的作用规律以及相应的物理模型.在此基础上,从细胞的黏性流动及力学平衡两个方面出发,简要综述了已有相关研究结果的不足之处,介绍了当前建立细胞铺展动力学模型的主要思路,并探讨了今后面向细胞生物学需求的相关细胞动力学的研究方向.      

Model for Elastic Modulus of Multi-Constituent Particulate Composites

In this paper, a methodology has been developed to accurately predict the elastic properties of multi-constituent particulate composites by accounting for irreversible effects, such as energy loss that arises due to internal friction. The complex dependence on loading density and particle properties (i.e., size, shape, morphology, etc.) is investigated in terms of their effects on the effective elastic modulus of the composite. Confirmed by experimental data from the compression loading of individual Ni and Al particles dispersed in an epoxy matrix, it is believed that this approach captures the effects of internal friction, consequently providing a more accurate and comprehensive representation for predicting and understanding the material behavior of multi-constituent particulate reinforced composites. The present methodology provides a model to directly compare the elastic modulus from an uncomplicated test, such as dual-cantilever beam loading in dynamic mechanical analysis (DMA), to the modulus obtained by other more complex experimental methods such as quasi-static compression. The model illustrates an efficient method to incorporate input data from DMA to represent realistic elastic moduli, hence promising for the characterization and design of particulate composites.     

Thermo-elastic optimization of material distribution of functionally graded structures by an isogeometrical approach

A new isogeometrical procedure for optimization of material composition of functionally graded structures in thermo-mechanical processes is introduced. The proposed method employs a generalized form of the standard isogeometric analysis method, allowing for gradation of material properties through patches. The variations of material properties are captured in a fully isogeometric formulation using the same NURBS basis functions employed for construction of the geometry and approximation of the solution. Subsequently, the applicates of control points that define the surfaces of volume fractions of the constituents are considered as the design variables and obtained by solving the optimization problem using a mathematical programming algorithm. Some numerical examples under thermal and mechanical loadings are considered to demonstrate the performance and applicability of the proposed method. Comparison of the obtained results with those of the other existing approaches such as finite elements and meshfree methods verifies the presented results. It will be seen that the proposed procedure considerably removes the difficulties of the existing methods and provides a promising tool for material design of functionally graded structures.     

NiTi形状记忆合金丝力学性能试验研究

形状记忆合金(SMA)是一种具有多种特性的新兴功能材料,其力学性能与材料本身的元素组成比例、应力状态以及周围的环境温度等有着复杂的关系．本文选用某金属开发有限公司生产的镍钛SMA为研究对象,对12组48根奥氏体状态下形状记忆合金丝试件进行力学性能试验,通过改变电流、加载幅值、加载速率、循环次数和直径等主要试验参数,研究了形状记忆合金材料的力学特性．结果表明：加载幅值和加载速率是影响奥氏体SMA材料力学性能的主要参数．     

On the dynamic mechanical properties of open-cell metal foams – A re-assessment of the ‘simple-shock theory’

Metal foams are increasingly used for energy absorption especially in lightweight structures and to resist blast and impact loads. This requires an understanding of the dynamic response of these materials for modelling purposes. As a supplement to Tan et al., 2005a, Tan et al., 2005b, hereinafter referred to as T–L for brevity, this paper provides experimental data for the dynamic mechanical properties of open-cell Duocel® foams having a three-dimensional (3D) distribution of cells. These confirm significant enhancement of the foam’s compressive strength, accompanied by changes in their deformation pattern in certain loading régimes, particularly what has come to be described as the ‘shock’ régime by Zheng et al. (2012). This paper examines experimentally, in a similar fashion as T–L, how the structural response of the individual cell walls is affected by cell-shape anisotropy at the cell (meso)-scale and how this, in turn, alters the pattern of cell crushing and the dynamic, mechanical properties. The distinctive role of cell microinertia and ‘shock’ formation are discussed in relation to the mechanical properties measured for these 3D cylindrical specimens. For consistency the same procedures described in T–L are used. The features identified are shown to be consistent with those observed in finite-element simulations of two-dimensional (2D) honeycombs as estimated by the one-dimensional (1D) steady-shock theory summarised in T–L. The different deformation patterns that develop in the various loading régimes are categorised according to the compression rate/impact speed. Critical values of impact velocity, corresponding to the transition from one pattern to the other, are quantified and predictive formulae for the compressive uniaxial strengths in the directions of two of the principal axes of the material in each loading régime are derived and discussed. The accuracy of the predictive formula in T–L is shown to critically depend on the ‘densification strain’ of the foam specimens. This parameter and the discussion that follows could assist the formulation and validation of alternative theoretical/computational models on the dynamic deformation of such materials.     

在材料研制中的连续介质细观力学有限元建模现状评论（译文）

评述了机械载荷下材料力学行为有限元模拟的先进技术.分析 了考虑材料微观及细观结构情况下，对材料变形、损伤、断裂进行模 拟时各种方法的优缺点及发展前景.阐述了对材料行为模拟方法的发 展，包括基本的及先进的方法，如体胞方法、真实结构模拟、粘结区 模型等.分析了在先进新材料的开发中运用有限元方法的可能性     

Discrete element simulation of effects of multicontact loading on single particle crushing

Particle crushing commonly occurs in granular materials and affects their structures and mechanical properties. Unlike idealized particles in experimental single particle crushing tests with two loading points, natural particles are crushed under multicontact loading. To date, the criteria and patterns of particle crushing under multicontact conditions are not fully understood. By using the three-dimensional discrete element method, this report explores the effect of multicontact loading on the crushing criterion of a single particle, the crushing pattern, and the relationship between the particle crushing strength and loading distribution. The particles are modelled as aggregates of glued Voronoi polyhedra. The numerical results indicate that the logarithm of the mean principal stress has a good linear correlation with the coordination number. For a specific coordination number, the number of child particles presents a significant normal distribution. For a specific number of child particles, the volumes of child particles can be statistically described as normal or gamma distribution. Three typical models are proposed to qualitatively analyse the relationship between the loading distribution and crushing strength. The relevant conclusions can be helpful in engineering practice and in further studies on crushable granular materials via the discrete element method.     

两种再生粗骨料混凝土单轴受压性能研究

为研究影响再生混凝土力学性能的因素,将建筑结构中使用最为广泛的C30与C40两种强度等级的废混凝土破碎成再生粗骨料RCA(recycled coarse aggregate),根据实测RCA吸水率调整了配合比。以RCA来源和RCA取代率为变量,设计了9组再生混凝土试件,进行立方体抗压强度及棱柱体单轴受压试验。基于试验数据,得到了两种不同来源RCA的再生混凝土弹性模量、峰值应变等重要力学性能参数,绘制了再生混凝土应力-应变曲线。结果表明,随着RCA取代率的增加,两种不同来源RCA再生混凝土弹性模量和立方体抗压强度均表现为下降,RCA强度对再生混凝土各项力学性能均有影响。     

Strain localization analysis for planar polycrystals based on bifurcation theory

In the present paper, an efficient numerical tool is developed to investigate the ductility limit of polycrystalline aggregates under in-plane biaxial loading. These aggregates are assumed to be representative of very thin sheet metals (with typically few grains through the thickness). Therefore, the plane-stress assumption is naturally adopted to numerically predict the occurrence of strain localization. Furthermore, the initial crystallographic texture is assumed to be planar. Considering the latter assumptions, a two-dimensional single-crystal model is advantageously chosen to describe the mechanical behavior at the microscopic scale. The mechanical behavior of the planar polycrystalline aggregate is derived from that of single crystals by using the full-constraint Taylor scale-transition scheme. To predict the occurrence of localized necking, the developed multiscale model is coupled with bifurcation theory. As will be demonstrated through various numerical results, in the case of biaxial loading under plane-stress conditions, the planar single-crystal model provides the same predictions as those given by the more commonly used three-dimensional single-crystal model. Moreover, the use of the two-dimensional model instead of the three-dimensional one allows dividing the number of active slip systems by two and, hence, significantly reducing the CPU time required for the integration of the constitutive equations at the single-crystal scale. Furthermore, the planar polycrystal model seems to be more suitable to study the ductility of very thin sheet metals, as its use allows us to rigorously ensure the plane-stress state, which is not always the case when the fully three-dimensional polycrystalline model is employed. Consequently, the adoption of this planar formulation, instead of the three-dimensional one, allows us to simplify the computational aspects and, accordingly, to considerably reduce the CPU time required for the numerical predictions.