Department of Mathematics, University of Sussex, Brighton BN1 9QH, UK.
Department of Mathematics, University of British Columbia, Vancouver, BC V6T 1Z2, Canada.
J Theor Biol. 2019 Nov 21;481:119-135. doi: 10.1016/j.jtbi.2018.09.008. Epub 2018 Sep 8.
Several cellular activities, such as directed cell migration, are coordinated by an intricate network of biochemical reactions which lead to a polarised state of the cell, in which cellular symmetry is broken, causing the cell to have a well defined front and back. Recent work on balancing biological complexity with mathematical tractability resulted in the proposal and formulation of a famous minimal model for cell polarisation, known as the wave pinning model. In this study, we present a three-dimensional generalisation of this mathematical framework through the maturing theory of coupled bulk-surface semilinear partial differential equations in which protein compartmentalisation becomes natural. We show how a local perturbation over the surface can trigger propagating reactions, eventually stopped in a stable profile by the interplay with the bulk component. We describe the behavior of the model through asymptotic and local perturbation analysis, in which the role of the geometry is investigated. The bulk-surface finite element method is used to generate numerical simulations over simple and complex geometries, which confirm our analysis, showing pattern formation due to propagation and pinning dynamics. The generality of our mathematical and computational framework allows to study more complex biochemical reactions and biomechanical properties associated with cell polarisation in multi-dimensions.
许多细胞活动,如定向细胞迁移,都是通过复杂的生化反应网络协调的,这些反应导致细胞处于极化状态,打破了细胞的对称性,使细胞具有明确的前后之分。最近,为了使生物复杂性与数学可处理性达到平衡,人们提出并建立了一个著名的细胞极化最小模型,即波钉扎模型。在这项研究中,我们通过成熟的耦合体-面半线性偏微分方程理论,对这个数学框架进行了三维推广,在该理论中,蛋白质分隔变得自然。我们展示了表面上的局部扰动如何引发传播反应,最终通过与体成分的相互作用在稳定的轮廓处停止。我们通过渐近和局部扰动分析来描述模型的行为,在该分析中,我们研究了几何形状的作用。我们使用体-面有限元方法对简单和复杂的几何形状进行数值模拟,这些模拟证实了我们的分析,显示了由于传播和钉扎动力学而导致的图案形成。我们的数学和计算框架的通用性允许在多维空间中研究与细胞极化相关的更复杂的生化反应和生物力学特性。