考虑细胞外基质黏弹性行为的细胞黏附力学模型

细胞外基质由大量胶原蛋白和纤维蛋白组成,这些基质蛋白形成复杂的交联网络状结构,具有黏弹性力学特性.研究表明,黏弹性基质能显著影响细胞迁移、增殖和分化等生理行为,还能影响癌症转移和组织纤维化等疾病的发生与发展.然而,细胞感知细胞外基质黏弹性力学特性的分子机制仍不清楚.该文通过建立细胞黏附力学模型,从分子层次揭示细胞黏附在细胞响应外界黏弹性力学微环境中的作用.结果表明,细胞能通过调控细胞黏附动力学（包括黏附周期和黏附形成时间）响应细胞外基质的黏弹性力学特性.通过将模型计算结果与实验现象相比较,验证了模型的正确性.细胞黏附力学模型将为组织工程中细胞力学微环境的构建奠定理论基础.     

一类具Rotenberg模型解的存在性

迁移方程是研究物质中的粒子运动所产生的微观效应综合所致的宏观迁移现象规律的一种模型,研究这类迁移方程对数学基础理论的发展有着非常重要的意义.在L_1空间中,运用线性算子理论,研究了种群细胞增生中具Rotenberg模型的迁移方程,采用所谓的豫解算子等法证明了种群细胞增生中具Rotenberg模型解的存在性.     

种群细胞增生中一类Rotenberg模型研究

本文在Lp（1（≤）p＜＋∞）空间上,研究了种群细胞增生中一类具非光滑边界条件的Rotenberg模型,讨论了这类模型相应的迁移算子的谱分析,证明了该迁移算子的本征值的存在性,得到了该迁移算子的谱在某半平面上仅由有限个具有限代数重数的离散本征值组成等结果.     

一类增生扩散型种群细胞中迁移方程的谱问题

在Lp(1≤p＜+∞)空间上,研究了一类具年龄结构的增生扩散型种群细胞中具无限周长的迁移方程,讨论了这类方程相应的迁移算子的谱,证明了在某个半平面该迁移算子的谱仅由可数个具有限代数重数的离散本征值组成等结果.     

细胞骨架与细胞外基质的力学建模与分析

细胞和生物组织需要适应人体内复杂的力学生物学环境,一方面要被动地承受外部环境中的机械力,另一方面在组织生长、修复等生理过程中要积极主动地产生机械力调整自身的结构和形态.细胞和生物组织的力学性质主要由细胞骨架和细胞外基质决定,它们在微观上都是生物聚合物交联形成的复杂的、各向异性的三维网络结构.这方面早期的力学研究主要集中在通过各种网络模型,理解其普遍存在的非线性响应和硬化行为.近年来随着实验方法、理论建模和计算机模拟技术的大幅进步,这些生命介质的力学性质及其潜在的力学机理得到了更深入的理解.该文回顾了近些年细胞骨架和细胞外基质研究方面取得的部分进展,主要侧重动态交联属性、生物聚合物力学化学耦合赋予的主动材料属性、交联网络塑性和断裂,以及力学训练引发的自适应网络重构.发展细胞骨架与细胞外基质的力学模型与计算方法,分析该类生命介质的复杂力学行为,理解这些力学行为的潜在机制,可以加深我们对细胞和组织的力学生物学认识,并为人造生物材料和细胞组织工程提供基础和参考.     

二维离散数学模型模拟肿瘤内外血管生成

建立九点差分格式的二维离散数学模型,模拟肿瘤内外的血管生成,模型扩展了内皮细胞沿9个方向运动,考虑存在两根母血管的情况下,耦合内皮细胞在肿瘤内外不同力学环境下的随机、趋化和趋触性运动,数值生成了肿瘤内外异构的血管网.结果表明,该模型可以产生相对真实的具有接近肿瘤病理生理特性的血管网,可为临床研究提供有益的信息.     

功能梯度板的柱面弯曲弹性力学解

在推广后的England-Spencer功能梯度板理论基础上,研究了功能梯度板在不同荷载作用下的柱面弯曲问题.采用该理论中的位移展开公式,并且材料参数沿板厚方向可以任意连续变化,并将材料由各向同性推广到正交各向异性.假设板在y方向无限长,最终建立了一个从弹性力学理论出发的正交各向异性功能梯度板在横向分布荷载作用下柱面弯曲问题的板理论.通过算例分析,讨论了边界条件、材料梯度及板厚跨比等因素对功能梯度板静力响应的影响.     

受约束高分子链的拉伸

高分子生物材料微观力学性质的定量刻画,以及先进生物微纳米技术与器件的发展均需要定量分析生物大分子等高分子链在复杂微环境中的统计热力学性质与行为.在实现这一目标的过程中,连续介质力学与统计热力学的交叉研究扮演着很重要的角色.针对这一领域的力学问题,该综述先从DNA分子的受力拉伸出发,通过引入描述高分子链统计热力学性质的几类理论模型,指出了蠕虫链相较其他理想随机链模型在描述半柔性高分子链力与构型变化关系时具有较为显著的优势,从而使得人们对高分子在复杂微环境下,统计热力学性质与行为的定性与定量认识在很大程度上取决于基于蠕虫链模型的相关研究进展.根据这一事实,通过回顾与梳理空间几何约束对高分子链随机构象分布影响、高分子链在拉力与约束同时作用时的统计热力学建模、以及基于高性能计算机的高分子链统计物理性质仿真等各方面研究的现状,系统总结了蠕虫链在不同约束与受力微环境下,其统计热力学性质与行为研究的最新进展和依旧存在的挑战性难题.最后,通过总结分析,指出了蠕虫链在复杂微环境下的统计热力学研究是从分子与细胞尺度理解生命现象、发展先进微纳米技术以及构建软物质本构关系的重要基础,目前已成为极富挑战性的力学交叉科学前沿课题.     

功能梯度板柱面弯曲的弹性力学解

利用推广后的Main和Spencer功能梯度板理论,研究了功能梯度矩形板在均布荷载作用下的柱面弯曲问题.采用该理论中的位移展开公式,并且材料参数沿板厚方向可以任意连续变化,但将材料由各向同性推广到正交各向异性,以及由不考虑板的横向荷载作用发展到受横向均布荷载作用.假设板在y方向无限长,从而得到了一个从弹性力学理论出发的正交各向异性功能梯度板在横向均布荷载作用下柱面弯曲问题的板理论.通过算例分析,讨论了边界条件和梯度变化程度对功能梯度板静力响应的影响.     

种群细胞中一类迁移算子的谱分析

在L~p(1≤p+∞)空间上,研究了种群细胞中一类具扰动项的L-R模型的迁移方程,证明了这类模型相应的迁移算子产生的正C_0半群是紧的,从而得到了该迁移算子的谱仅由可数个具有限代数重数的离散本征值组成,且-∞是唯一可能的聚点等结果.     

Stochastic transitions in a mathematical model for capillary network formation

In a model of cell migration in the presence of chemotaxis and haptotaxis, bimodal density distributions can be induced by noise. We suggest this phenomenon as a possible explanation of the experimentally observed up and down motion of the endothelial cells in tumour-related angiogenesis.     

A mathematical analysis of a model for capillary network formation in the absence of endothelial cell proliferation

An analysis of a parabolic partial differential equation modelling capillary network formation is presented. The model includes terms representing cell random motility, chemotaxis, and haptotaxis due to the presence of chemical stimuli: tumour angiogenic factors and fibronectin. The analysis provides an underlying insight into mechanisms of cell migration which are crucial for tumour angiogenesis. Specific 1 and 2D examples are discussed in detail.     

A unified term for directed and undirected motility in collective cell invasion

In this paper, we develop mathematical models for collective cell motility. Initially we develop a model using a linear diffusion–advection type equation and fit the parameters to data from cell motility assays. This approach is helpful in classifying the results of certain cell motility assay experiments. In particular, this model can determine degrees of directed versus undirected collective cell motility. Next we develop a model using a nonlinear diffusion term that is able to capture in a unified way directed and undirected collective cell motility. One goal of this work is to demonstrate that the forms of collective cell motility seen in the scratch assays and possibly other systems of interest need not reference external and more complicated migratory signals such as chemotaxis, but rather could be based on quorum sensing alone, collectively represented as density-dependent diffusivity. As an application we apply the nonlinear diffusion approach to a problem in tumor cell invasion, noting that neither chemotaxis or haptotaxis are present in the system under consideration in this article.     

A second-order positivity preserving central-upwind scheme for chemotaxis and haptotaxis models

The paper is concerned with development of a new finite-volume method for a class of chemotaxis models and for a closely related haptotaxis model. In its simplest form, the chemotaxis model is described by a system of nonlinear PDEs: a convection-diffusion equation for the cell density coupled with a reaction-diffusion equation for the chemoattractant concentration. The first step in the derivation of the new method is made by adding an equation for the chemoattractant concentration gradient to the original system. We then show that the convective part of the resulting system is typically of a mixed hyperbolic-elliptic type and therefore straightforward numerical methods for the studied system may be unstable. The proposed method is based on the application of the second-order central-upwind scheme, originally developed for hyperbolic systems of conservation laws in Kurganov et al. (SIAM J Sci Comput 21:707–740, 2001), to the extended system of PDEs. We show that the proposed second-order scheme is positivity preserving, which is a very important stability property of the method. The scheme is applied to a number of two-dimensional problems including the most commonly used Keller–Segel chemotaxis model and its modern extensions as well as to a haptotaxis system modeling tumor invasion into surrounding healthy tissue. Our numerical results demonstrate high accuracy, stability, and robustness of the proposed scheme.     

On generalized gradients

In this paper we present a concept of the construction of generalized gradients by considering a development of directional derivatives into spherical harmonics. This leads to a derivation system as a system of generalized partial derivatives. Necessary conditions for local extrema for a broad class of not necessarily differentiable function can be given and a characterization of points of differentiability can be proved by using generalized gradients.     

Global existence for a haptotaxis model of cancer invasion with tissue remodeling

This paper considers a 3×3 haptotaxis model of cancer invasion with tissue remodeling. The model consists of a parabolic haptotaxis partial differential equation (PDE) describing the evolution of tumor cell density, an ordinary differential equation modeling the proteolysis and the remodeling of the extracellular matrix (ECM), and a parabolic PDE governing the evolution of the matrix degrading enzyme (MDE) concentration. In addition to random diffusion, tumor cells are biased towards higher ECM density, which is referred to as haptotaxis. Under a restrictive assumption on the coefficients, the global existence and uniqueness of classical solutions to the model in two dimensions, along with the boundedness of solutions in two and three dimensions, is proved by establishing some delicate a priori estimates.     

A note on sensitivity of value functions of mathematical programs with complementarity constraints

Using standard nonlinear programming (NLP) theory, we establish formulas for first and second order directional derivatives of optimal value functions of parametric mathematical programs with complementarity constraints (MPCCs). The main point is that under a linear independence condition on the active constraint gradients, optimal value sensitivity of MPCCs is essentially the same as for nonlinear programs, in spite of the combinatorial nature of the MPCC feasible set. Unlike NLP however, second order directional derivatives of the MPCC optimal value function show combinatorial structure. Received: October 31, 2000 / Accepted: March 8, 2002?Published online June 25, 2002     

High-order positivity-preserving hybrid finite-volume-finite-difference methods for chemotaxis systems

Chemotaxis refers to mechanisms by which cellular motion occurs in response to an external stimulus, usually a chemical one. Chemotaxis phenomenon plays an important role in bacteria/cell aggregation and pattern formation mechanisms, as well as in tumor growth. A common property of all chemotaxis systems is their ability to model a concentration phenomenon that mathematically results in rapid growth of solutions in small neighborhoods of concentration points/curves. The solutions may blow up or may exhibit a very singular, spiky behavior. There is consequently a need for accurate and computationally efficient numerical methods for the chemotaxis models. In this work, we develop and study novel high-order hybrid finite-volume-finite-difference schemes for the Patlak-Keller-Segel chemotaxis system and related models. We demonstrate high-accuracy, stability and computational efficiency of the proposed schemes in a number of numerical examples.     

Statistical analysis of the intermediate filament network in cells of mesenchymal lineage by greyvalue-oriented image segmentation

Intermediate filament networks are part of the cytoskeleton and protect cellular integrity during large deformations. In cells from mesenchymal lineage the cytoskeleton is centrally involved in signal transduction, thereby influencing differentiation. We study the ultrastructure of IF networks in three human mesenchymal cell types, namely undifferentiated mesenchymal stem cells, chondrocytes, and osteoblasts. In order to capture the high morphological variability of IF networks we apply techniques from image analysis to extract the network graph from 2D scanning electron microscopy (SEM) images in a fully automatic way, which allows for a high-throughput analysis of SEM data. The extracted network graphs are analyzed by techniques from spatial statistics to detect differences in network morphology between different cell types and infer strategies of network remodeling used by the cells to adapt their mechanical properties during migration and differentiation.