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用于通过通用生长函数描述二维集体细胞铺展的随机模拟工具和连续体模型。

Stochastic simulation tools and continuum models for describing two-dimensional collective cell spreading with universal growth functions.

作者信息

Jin Wang, Penington Catherine J, McCue Scott W, Simpson Matthew J

机构信息

School of Mathematical Sciences, Queensland University of Technology (QUT), Brisbane, Australia.

出版信息

Phys Biol. 2016 Oct 7;13(5):056003. doi: 10.1088/1478-3975/13/5/056003.

Abstract

Two-dimensional collective cell migration assays are used to study cancer and tissue repair. These assays involve combined cell migration and cell proliferation processes, both of which are modulated by cell-to-cell crowding. Previous discrete models of collective cell migration assays involve a nearest-neighbour proliferation mechanism where crowding effects are incorporated by aborting potential proliferation events if the randomly chosen target site is occupied. There are two limitations of this traditional approach: (i) it seems unreasonable to abort a potential proliferation event based on the occupancy of a single, randomly chosen target site; and, (ii) the continuum limit description of this mechanism leads to the standard logistic growth function, but some experimental evidence suggests that cells do not always proliferate logistically. Motivated by these observations, we introduce a generalised proliferation mechanism which allows non-nearest neighbour proliferation events to take place over a template of [Formula: see text] concentric rings of lattice sites. Further, the decision to abort potential proliferation events is made using a crowding function, f(C), which accounts for the density of agents within a group of sites rather than dealing with the occupancy of a single randomly chosen site. Analysing the continuum limit description of the stochastic model shows that the standard logistic source term, [Formula: see text], where λ is the proliferation rate, is generalised to a universal growth function, [Formula: see text]. Comparing the solution of the continuum description with averaged simulation data indicates that the continuum model performs well for many choices of f(C) and r. For nonlinear f(C), the quality of the continuum-discrete match increases with r.

摘要

二维集体细胞迁移分析用于研究癌症和组织修复。这些分析涉及细胞迁移和细胞增殖过程的结合,这两个过程均受细胞间拥挤的调节。以前的集体细胞迁移分析离散模型涉及最近邻增殖机制,其中如果随机选择的目标位点被占据,则通过中止潜在的增殖事件来纳入拥挤效应。这种传统方法有两个局限性:(i)基于单个随机选择的目标位点的占据情况中止潜在的增殖事件似乎不合理;以及,(ii)该机制的连续极限描述导致标准逻辑斯谛增长函数,但一些实验证据表明细胞并不总是按逻辑斯谛方式增殖。受这些观察结果的启发,我们引入了一种广义增殖机制,该机制允许非最近邻增殖事件在由[公式:见正文]个晶格位点同心环组成的模板上发生。此外,使用拥挤函数f(C)来决定是否中止潜在的增殖事件,该函数考虑了一组位点内的主体密度,而不是处理单个随机选择位点的占据情况。对随机模型的连续极限描述进行分析表明,标准逻辑斯谛源项[公式:见正文](其中λ是增殖率)被推广为通用增长函数[公式:见正文]。将连续描述的解与平均模拟数据进行比较表明,对于f(C)和r的许多选择,连续模型表现良好。对于非线性f(C),连续-离散匹配的质量随r增加。

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