Probing the mechanosensitivity in cell adhesion and migration: Experiments and modeling

Cell adhesion and migration are basic physiological processes in living organisms. Cells can actively probe their mechanical micro-environment and respond to the external stimuli through cell adhesion. Cells need to move to the targeting place to perform function via cell migration. For adherent cells, cell migration is mediated by cell-matrix adhesion and cell-cell adhesion. Experimental approaches, especially at early stage of investigation, are indispensable to studies of cell mechanics when even qualitative behaviors of cell as well as fundamental factors in cell behaviors are unclear. Currently, there is increasingly accumulation of experimental data of measurement, thus a quantitative formulation of cell behaviors and the relationship among these fundamental factors are highly needed. This quantitative understanding should be crucial to tissue engineering and biomedical engineering when people want to accurately regulate or control cell behaviors from single cell level to tissue level. In this review, we will elaborate recent advances in the experimental and theoretical studies on cell adhesion and migration, with particular focuses laid on recent advances in experimental techniques and theoretical modeling, through which challenging problems in the cell mechanics are suggested.     

STICTION AND ANTI—STICTION IN MEMS AND NEMS

Stiction in microelectromechanical systems (MEMS) has been a major failure mode ever since the advent of surface micromachining in the 80s of the last century due to large surfacearea-to-volume ratio. Even now when solutions to this problem are emerging, such as self-assembled monolayer (SAM) and other measures, stiction remains one of the most catastrophic failure modes in MEMS. A review is presented in this paper on stiction and anti-stiction in MEMS and nanoelectromechanical systems (NEMS). First, some new experimental observations of stiction in radio frequency (RF) MEMS switch and micromachined accelerometers are presented. Second, some criteria for stiction of microstructures in MEMS and NEMS due to surface forces (such as capillary, electrostatic, van der Waals, Casimir forces, etc.) are reviewed. The influence of surface roughness and environmental conditions (relative humidity and temperature) on stiction are also discussed. As hydrophobic films, the self-assembled monolayers (SAMs) turn out able to prevent release-related stiction effectively. The anti-stiction of SAMs in MEMS is reviewed in the last part. The project supported by the Distinguished Young Scholar Fund of NSFC (10225209), key project from the Chinese Academy of Sciences (KJCX2-SW-L2) and National “973” Project (G1999033103)     

微机械IMU数据建模与滤波方法研究

针对轮式移动机器人内部的微机械（MEMS）IMU进行研究，采用时间序列分析方法建立其随机噪声的ARMA模型，进而通过Kalman滤波有效地降低MEMSIMU随机噪声对其精度的影响，频域分析结果表明文中建模和滤波方法对提高MEMSIMU精度的有效性。     

力学实验教学示范中心建设与发展中的探索与实践

本文对力学实验教学示范中心的建设内容进行了探索性的研究,介绍了同济大学力学实验中心在建设实验教学示范中心过程中的一些探索实践与体会,希望其中一些有益的经验和实验建设内容能与同仁分享和交流。     

Modeling MEMS resonators with rod-like components accounting for anisotropy, temperature, and strain dependencies

Numerous systems can be described using masses and rods in transverse vibration. Motivated by the desire to model the effects of axial strain and temperature on systems of this type, we develop a procedure to determine the frequencies of transverse vibration of devices composed of rods and rigid masses as functions of these effects. Our models allow for the rods to be composed of anisotropic materials with material symmetry contained in the cubic system. The goal of the present paper is to demonstrate the modeling procedure using the example of a double-ended tuning fork (DETF). Following this, the results of a slightly more complicated model are compared with the experimental results found for a prototype MEMS DETF sensor composed of polycrystalline silicon.     

基于MEMS加速度计的倒置开关

运用MEMS加速度计MMA8453Q和单片机MSP430设计了一种针对放入式电子测压器的倒置开关。利用加速度计方向检测功能,单片机通过I2C接口读取加速度,判断是否倒置。倒置开关经步进电机多次旋转倒置测试成功率达到100%,并利用霍普金森杆进行了抗过载测试。结果表明,在受到45000g 冲击后仍能正常工作,能满足火炮等高冲击场合的测试要求。     

Cell polarization energy and its implications for cell migration

Cells usually have a polarized shape in directional cell migration. This cell polarity may result from external cues, such as a gradient of chemo-attractants (chemotaxis), or a gradient of mechanical properties of substrate (durotaxis), and it can also arise from internal cues so that the cells self-polarize spontaneously and maintain the polar motile state for a long time. However, the mechanisms that control cell polarization have not been fully understood, and particularly, the relationship between the polarized shape and cell migration behaviors is not yet clear. In this study, we propose an energy model to study the cell polarization energy by considering the effect of matrix rigidity, cell shape, and organization of the cytoskeleton. We then propose a parameter called “motility factor” for depicting the relationship between the cell shape and the driving force of cell migration. We demonstrate that the fibroblast-like cell shape and keratocyte-like shape both have an optimal polarization angle corresponding to the most stable cell shape. Fibroblast-like cell shape also has an optimal tail length of the polarization. Furthermore, we find that the cell free energy biphasically depends on the matrix rigidity, i.e. that there is an optimum matrix rigidity for the most stable shape. And the motility factor also biphasically depends on the matrix rigidity, but the trends of the dependence are opposite to that of cell's free energy, which implies an optimum matrix rigidity for the highest speed. The optimum matrix rigidity for the most stable cell shape and that for the highest cell speed are consistent, suggesting that the most stable cell shape is favorable to the fastest cell migration. This study provides important insights into the relationship between cell polarization shape and cell migration behaviors.     

Mechanics Applied to Skeletal Ontogeny and Phylogeny

The musculo-skeletal system serves the mechanical function of creating motion and transmitting loads. It is made up mainly of four components: bone, cartilage, muscle and fibrous connective tissue. These have evolved over millions of years into the complex and diverse shapes of the animal skeleton. The skeleton, however, is not built to a static plan: it can adapt to mechanical forces during growth, it can remodel if the forces change, and it can regenerate if it is damaged. In this paper, the regulation of skeletal construction by mechanical forces is analyzed from both ontogenetic and phylogenetic standpoints. In the first part, models of biomechanical processes that act during skeletal ontogenesis – tissue differentiation and bone remodeling – are presented and, in the second, the evolution of the middle ear is used as an example of biomechanical change in skeletal phylogenesis. Because the constitutive laws for skeletal tissues are relatively well understood, and because the skeleton is preserved in the fossil record, application of mechanics to skeletal evolution seems to present a good opportunity to explore the relationships governing ontogenetic adaptations and phylogenetic change.     

Two-dimensional model of vesicle adhesion on curved substrates

We develop a two dimensional model of a vesicle adhered on a curved substrate via long-range molecular interactions while subjected to a detachment force. The relationship between the force and displacement of the vesicle is investigated as a function of the substrate shape. It is shown that both the force– displacement relationship and the maximum force at pull-off are significantly dependent on the substrate shape. The results suggest that probes with different tip shapes may be designed for cell manipulation. For example, we demonstrate that a vesicle can be pulled off a flat surface using a probe with a curved tip.The project supported by the National Natural Science Foundation of China (10525210 and 10121202) and the 973 Program.     

Continuum Mechanics Modeling and Simulation of Carbon Nanotubes

The understanding of the mechanics of atomistic systems greatly benefits from continuum mechanics. One appealing approach aims at deductively constructing continuum theories starting from models of the interatomic interactions. This viewpoint has become extremely popular with the quasicontinuum method. The application of these ideas to carbon nanotubes presents a peculiarity with respect to usual crystalline materials: their structure relies on a two-dimensional curved lattice. This renders the cornerstone of crystal elasticity, the Cauchy–Born rule, insufficient to describe the effect of curvature. We discuss the application of a theory which corrects this deficiency to the mechanics of carbon nanotubes (CNTs). We review recent developments of this theory, which include the study of the convergence characteristics of the proposed continuum models to the parent atomistic models, as well as large scale simulations based on this theory. The latter have unveiled the complex nonlinear elastic response of thick multiwalled carbon nanotubes (MWCNTs), with an anomalous elastic regime following an almost absent harmonic range.     

SEM扫描云纹法相移技术在MEMS中的应用

本文提出一种扫描电镜（SEM）扫描云纹法的相移新技术，通过SEM系统控制电镜电子束扫描线移动，对获取的云纹图像实现0－2π范围内的四步相移，从而获得了更高的位移测量灵敏度，同时对SEM相移实验技术的原理进行了详细的阐述，并将该技术应用到微电子机械系统构件的虚应变分析中，实验结果证明了该方法的可行性，该方法为微米云纹法的条纹处理提供了一种新途径。     

蠕动爬行微电机械力－电耦合的致动特性分析

对于以施加电场作为驱动的蠕动爬行微电机构，在柔韧薄板理论和电学物理基础上，通过考虑驱动元件在电场力作用下的几何非线性变形和与结构变形相关的电荷分布及电场力分布，建立了其驱动元件的非线性耦合模型。在此基础上，采用矩量法和增量有限元法相结合，给出了其微电机构在失稳前由弯曲变形引起的蠕动距离随外加电压之间的特征关系。     

Stress field at a sliding frictional contact: Experiments and calculations

A MEMS-based sensing device is used to measure the normal and tangential stress fields at the base of a rough elastomer film in contact with a smooth glass cylinder in steady sliding. This geometry allows for a direct comparison between the stress profiles measured along the sliding direction and the predictions of an original exact bidimensional model of friction. The latter assumes Amontons’ friction law, which implies that in steady sliding the interfacial tangential stress is equal to the normal stress times a pressure-independent dynamic friction coefficient μ_d, but makes no further assumption on the normal stress field. Discrepancy between the measured and calculated profiles is less than 14% over the range of loads explored. Comparison with a test model, based on the classical assumption that the normal stress field is unchanged upon tangential loading, shows that the exact model better reproduces the experimental profiles at high loads. However, significant deviations remain that are not accounted for by either calculations. In that regard, the relevance of two other assumptions made in the calculations, namely (i) the smoothness of the interface and (ii) the pressure-independence of μ_d is briefly discussed.     

剪切载荷作用下植物细胞的力学特性分析

根据植物细胞的结构特点,以二维问题为研究对象,在已建立的植物单细胞力学模型的基础上,利用有限元方法和MATLAB计算软件研究了单细胞受到剪切载荷作用时,外力、应力、应变及内压间的相互关系,给出了关系曲线图。得出了在剪切情况下,外力、应力、应变及内压之间的关系是非线性的;细胞内压改变量随外力或细胞变形或细胞壁应力的增加而增加;细胞壁的应力随剪切力的增大而增大;细胞将在哪个方向破裂等6个结论。     

上海市力学学会60年

上海市力学学会成立于1959年9月20日,到今年正好是一个甲子．60个春秋真实写照了上海市力学学会的建立、成长、发展与壮大的过程．60年来,在上海市科协的领导和中国力学学会的指导下,在各团体成员单位的大力支持下,上海市力学学会一代代力学工作者薪火相传、开拓耕耘,历届理事会及下属工作委员会和专业委员会团结奋进、不断创新,广大会员踊跃参与,为上海力学大力发展、力学人才精心培养、力学知识科学普及、力学服务国家发展战略和区域经济建设中做出了重要贡献,学会持续发展壮大．在庆祝力学学会成立六十周年之际,让我们共同抒怀上海力学六十年薪火相传、回顾近10年重要发展,展望上海力学新时代．     

MEMS动平板的切向静电阻力

由于微机械的表面积与体积之比远大于宏机械,所以微机械中的表面阻力难以忽略,为了改善MEMS器件的性能和可靠性,必须对其影响进行研究.基于能量守衡法,本文建立了光滑平板和正方形、四棱锥两种微凸体粗糙表面平板的切向静电阻力模型,讨论了微小尺度、表面形貌、外加电压以及因流片制造工艺而产生的微凸体、凹坑或孔对两个相对运动的带电平板间的切向静电阻力的影响.分析表明：当平板宽度与两平板之间的距离之比、表面形貌因数和外加电压增大时,切向静电阻力也将随之增加;表面形貌因数则与微凸体在平板的总投影面积与平板面积之比成正比,随相对表面粗糙度增加而非线性增加.     

The role of binder mobility in spontaneous adhesive contact and implications for cell adhesion

The standard view of mechanical adhesive contact is as a competition between a reduction in free energy when surfaces with bonding potential come into contact and an increase in free energy due to elastic deformation that is required to make these surfaces conform. An equilibrium state is defined by an incremental balance between these effects, akin to the Griffith crack growth criterion. In the case of adhesion of biological cells, the molecules that tend to form surface-to-surface bonds are confined to the cell wall but they are mobile within the wall, adding a new phenomenon of direct relevance to adhesive contact. In this article, the process of adhesive contact of an initially curved elastic plate to a flat surface is studied for the case in which the binders that account for adhesion are able to migrate within the plate. This is done by including entropic free energy of the binder distribution in the total free energy of the system. By adopting a constitutive assumption that binders migrate at a speed proportional to the local gradient in chemical potential, the transient growth of an adhesion zone due to binder transport is analyzed. For the case of a plate of very large extent, the problem can be solved in closed form, whereas numerical methods are invoked for the case of a plate of limited extent. Results are presented on the rate of growth of an adhesion zone in terms of system parameters, on the evolution of the distribution of binders and, in the case of a plate of limited extent, on the long-term limiting size of the adhesion zone.     

Snap transitions in adhesion

Equilibrium adhesion states are analyzed for nonlinear spherical caps adhered to a rigid substrate under the influence of adhesive tractions that depend on the local separation between the shell and substrate. Transitions between bistable snapped-in and snapped-out configurations are predicted as a function of four nondimensional parameters representing the adhesive energy, the undeformed shell curvature, the range of the adhesive interactions, and the magnitude of an externally applied load. Nonuniform energy and traction fields associated with free-edge boundary conditions are calculated to better understand localized phenomena such as the diffusion of impurities into a bonded interface and the diffusion of receptors in the cell membrane. The linear Griffith approximations commonly used in the literature are shown to be limited to shells with a small height to thickness ratio and short-range adhesive interactions. External loading is found to alter the adhered configurations and the spatial distributions of both adhesive and elastic energies. An important implication of the latter analysis is the theoretical prediction of the pull-off force, which is shown to depend not only on the interface properties, but also on the geometric and material parameters of the shell and on both the magnitude and type of external loading.     

微机械杠杆力放大效果的计算和提高

硅微谐振式加速度计是一种高精度的惯性传感器,它通过谐振梁刚度随惯性力的变化检测输入加速度的大小。为了得到较高的标度因数,国内外的研究机构普遍使用微机械杠杆机构来放大惯性力,但实验中微机械杠杆往往达不到理想的放大倍数,尤其是多级杠杆对力的放大作用非常有限。结合国内加工条件,微机械杠杆力放大机构的模型被合理简化,使用有限元分析运动模态的方法,分别计算微机械杠杆、检测质量支撑梁以及谐振梁的刚度,并按此仿真计算结果估算微机械杠杆的力放大倍数。通过理论推导、ANSYS仿真和对微机械杠杆实验的结果验证了这种方法的正确性。为分析微机械杠杆实际的力放大效果提供了一种实用方法,并基于此方法提出通过提高输出刚度来提高微机械杠杆力放大倍数的方法。通过对杠杆结构的优化,可将原有3.9倍的杠杆放大倍数提高到7.0倍。