Dirks Carolin, Striewski Paul, Wirth Benedikt, Aalto Anne, Olguin-Olguin Adan
WWU Münster FB 10 Mathematik und Informatik, Institute for Analysis and Numerics, 48149 Münster, Germany.
WWU Münster FB 13 Biologie, Institute of Cell Biology, Center for Molecular Biology of Inflammation, 48149 Münster, Germany.
Math Med Biol. 2021 Jun 15;38(2):218-254. doi: 10.1093/imammb/dqab002.
Blebs are cell protrusions generated by local membrane-cortex detachments followed by expansion of the plasma membrane. Blebs are formed by some migrating cells, e.g. primordial germ cells of the zebrafish. While blebs occur randomly at each part of the membrane in unpolarized cells, a polarization process guarantees the occurrence of blebs at a preferential site and thereby facilitates migration toward a specified direction. Little is known about the factors involved in the controlled and directed bleb generation, yet recent studies revealed the influence of an intracellular flow and the stabilizing role of the membrane-cortex linker molecule Ezrin. Based on this information, we develop and analyse a coupled bulk-surface model describing a potential cellular mechanism by which a bleb could be induced at a controlled site. The model rests upon intracellular Darcy flow and a diffusion-advection-reaction system, describing the temporal evolution from a homogeneous to a strongly anisotropic Ezrin distribution. We prove the well-posedness of the mathematical model and show that simulations qualitatively correspond to experimental observations, suggesting that indeed the interaction of an intracellular flow with membrane proteins can be the cause of the Ezrin redistribution accompanying bleb formation.
气泡是由局部细胞膜 - 皮层脱离，随后质膜扩张产生的细胞突起。气泡由一些迁移细胞形成，例如斑马鱼的原始生殖细胞。在非极化细胞中，气泡在膜的各个部分随机出现，而极化过程确保气泡在优先位点出现，从而促进细胞向特定方向迁移。关于参与受控和定向气泡生成的因素知之甚少，但最近的研究揭示了细胞内流动的影响以及膜 - 皮层连接分子埃兹蛋白（Ezrin）的稳定作用。基于这些信息，我们开发并分析了一个耦合的体 - 表面模型，该模型描述了一种潜在的细胞机制，通过该机制可以在受控位点诱导气泡。该模型基于细胞内达西流和一个扩散 - 对流 - 反应系统，描述了从均匀的埃兹蛋白分布到强烈各向异性分布的时间演化。我们证明了该数学模型的适定性，并表明模拟结果在定性上与实验观察结果相符，这表明细胞内流动与膜蛋白的相互作用确实可能是气泡形成时埃兹蛋白重新分布的原因。
