细胞力学传感系统

发布时间：2018-01-10 14:01

本文关键词：细胞力学传感系统　出处：《浙江大学》2016年博士论文　论文类型：学位论文

【摘要】：细胞力学传感系统的各部分结构(主要是应力纤维和粘附斑)如何通过其微纳米尺度上的分子活动相互配合来感知宏观的细胞外基底的力学环境并为之做出反应?这是近年来细胞力学领域关心的一个新兴课题。基于相关实验,研究者们对此进行了大量的理论建模和数值模拟,但至今仍然缺乏一个完整的细胞力学传感系统的模型来模拟并预测这一系统的随机动态行为。细胞粘附作为该系统中重要的组成部分,将细胞与细胞外基底直接连接。对细胞粘附的研究相对来讲较早开展,特别是均匀和各向同性材料调控细胞粘附的研究已经相对充分。在此基础上,我们运用了一个随机-弹性耦合模型分别研究了几类天然或人造材料,例如功能梯度材料、各向异性材料以及受预拉伸调控的高弹体,如何对细胞粘附产生定量影响。结果显示,这些材料作为基底时都可以有效地调控细胞粘附的动力学行为,包括细胞粘附的稳定性以及细胞粘附所产生的表面间摩擦力。由此我们可以推测生物体内具有相应力学性质的组织或细胞结构是如何调控细胞行为的。将这些材料应用于细胞或者组织工程,可以提供更加有效的、基于仿生原理的人造基底材料,以实现对细胞行为的更好调控。接着,在随机-弹性相互耦合的建模思想基础上,我们通过考虑应力纤维的收缩、合成和分解,以及粘附斑的多层结构、分子键的逆锁键特性、粘附斑的合成和分解等细胞力学传感系统的跨尺度结构和随机行为,建立了一个完整的、可以实时模拟细胞力学传感系统的动态行为——包括自身生长演化、对外界力学环境的感知——的随机-弹性耦合力学模型。我们用这个模型研究了细胞力学传感系统的生长过程,以及细胞外基底的曲率、刚度和循环变形等力学信号对该系统行为的影响。相关模拟结果直接或间接解释了许多之前无法解释的实验现象：比如细胞铺展过程中应力纤维-粘附斑复合体尺度会从小于一微米生长到与细胞同尺度的几十微米；抑制肌球蛋白导致应力纤维和粘附斑分解消失,恢复肌球蛋白导致粘附斑应力纤维系统重建,且这一过程双向可逆；微米尺度的细胞能够感知毫米尺度的基底曲率半径并产生响应；粘附斑中应力值大小基本不变以及外部载荷在一定范围内可以促进粘附斑的成熟等。这一跨尺度模型从单分子尺度的随机反应出发,跨越细胞和亚细胞尺度团簇结构的行为,且将细胞外基质的宏观力学性能考虑在内。通过与相关实验现象的比较,该模型可以比较完整地反应细胞力学传感系统的行为特性,并用于研究应力纤维和粘附斑介导的细胞力学行为。
[Abstract]:The structure of the cell mechanical sensing system (mainly stress fibers and focal adhesion) to cooperate with each other to perceive the macro mechanical environment outside the cell substrate and respond to its activities through molecular micro nano scales? This is an emerging issue of concern in the field of cell mechanics. Based on the experiments. The researchers conducted a lot of theoretical modeling and numerical simulation, but still lack of a complete system of sensing cell mechanical model to simulate and forecast the random dynamic behavior of this system. The cell adhesion is an important part of the system, the cell and extracellular substrate directly connected. Research on cell adhesion the relatively early development, especially the research of homogeneous and isotropic material in cell adhesion has been relatively full. On this basis, we use a stochastic - elastic coupling Model of several kinds of natural or artificial materials were studied, such as functional gradient materials, anisotropic materials and elastomers by pre tension control, how to generate quantitative effects on cell adhesion. The results show that these materials as the substrate can effectively control the dynamic behavior of cell adhesion, including cell adhesion between the friction surface stability and cell adhesion generated. Thus we can speculate that the organism has the corresponding mechanical properties of tissue or cell structure is how to regulate the behavior of cells. These materials will be used for cell or tissue engineering, can provide more effective, based on the principle of bionics artificial substrate material, in order to achieve better regulation of cell behavior. Then on the ideological basis of random modeling, elastic coupling, we stress fiber contraction by considering the synthesis and decomposition, and focal adhesion The key characteristics of multilayer structure, inverse molecular bond, multiscale structure and random behavior synthesis and decomposition of cell adhesion plaque mechanical sensing system, establish a complete and dynamic behavior of real-time simulation of cell mechanical sensing system -- including its evolution, on the outside of the mechanical environment perception -- stochastic elasticity the coupling mechanics model. We study the process of cell growth and mechanical sensing system using the model, and the curvature of extracellular substrate, the effect of stiffness and cyclic deformation mechanical signal to the behavior of the system. The simulation results directly or indirectly explained the experimental phenomena before many unexplained: stress fibers - focal adhesion complexes from less than a micron scale growth and cell scale to tens of microns such as cell spreading process; inhibiting myosin lead to stress fibers and focal adhesion decomposition Disappear, focal adhesion stress leads to recovery of myosin fiber system reconstruction, and this process is reversible; micron scale cells to the substrate curvature radius perception millimeter scale and generate response; stress value is basically unchanged and the external load in a certain range can promote adhesion plaque maturation in focal adhesion. This cross scale the model from the random response of single molecular scale of cellular and subcellular scale across the cluster structure and behavior, mechanical properties of the extracellular matrix into account. By comparing with the related experimental phenomena, behavior characteristics of the model can be more complete reaction cell mechanical sensor system, and used to study on the mechanical behavior of cells should be stress fibers and focal adhesion mediated.

【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：Q27;TP212

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