Protrusive push versus enveloping embrace: computational model of phagocytosis predicts key regulatory role of cytoskeletal membrane anchors.
Protrusive push versus enveloping embrace: computational model of phagocytosis predicts key regulatory role of cytoskeletal membrane anchors.
复制标题
突出的推动与包围拥抱：吞噬作用的计算模型预测了细胞骨架膜锚的关键调节作用。
DOI：
10.1371/journal.pcbi.1001068
复制
发表时间：
2011-01-27
影响因子：
4.3
通讯作者：
Heinrich V
中科院分区：
文献类型：
--
作者：
Herant M;Lee CY;Dembo M;Heinrich V
人中性粒细胞和酵母聚糖之间的相遇引起最初的扩散性细胞反应，这与包含抗体包被的靶的薄层不同。最近的实验使我们假设，这种行为有其机制的根源在膜和细胞骨架之间的相互作用的调制。为了测试和完善这一假设，我们面对我们的实验结果与白细胞机械行为的计算机模型的预测，并建立最小的机械变化的计算框架，再现酵母多糖和抗体吞噬作用之间的差异。我们证实，粘附到目标的细胞骨架和膜补丁之间的结构联系形成的“配电盘”，控制中性粒细胞的机械响应的目标特异性。这些连接可能是肌动蛋白结合蛋白复合物与细胞表面受体的胞质结构域相关联，这些受体参与与酵母聚糖和Fc结构域的粘附。最近的微量移液器实验提供了一个独特的“一对一”的人类中性粒细胞和它们的吞噬目标之间的相互作用的现场视图。我们的研究结果揭示了两个突出的免疫途径之间的惊人差异：对真菌靶点的反应（使用酵母多糖颗粒模拟）和抗体介导的吞噬作用。而抗体包被的目标是“拉”到细胞中以一种简单的方式，酵母多糖颗粒内化后，只有在最初的向外“推”。我们假设，细胞骨架和粘附到目标的膜补丁之间的结构相互作用在控制这种目标特异性中起着关键作用。为了验证和完善这一假设，我们在这里将我们的实验结果与先前验证的中性粒细胞机械行为计算模型的适当适应性预测进行比较。通过优化模型，以最好地匹配我们的实验，我们证实，靶特异性细胞行为的主要机制起源确实在于细胞骨架膜锚的强度。
Encounters between human neutrophils and zymosan elicit an initially protrusive cell response that is distinct from the thin lamella embracing antibody-coated targets. Recent experiments have led us to hypothesize that this behavior has its mechanistic roots in the modulation of interactions between membrane and cytoskeleton. To test and refine this hypothesis, we confront our experimental results with predictions of a computer model of leukocyte mechanical behavior, and establish the minimum set of mechanistic variations of this computational framework that reproduces the differences between zymosan and antibody phagocytosis. We confirm that the structural linkages between the cytoskeleton and the membrane patch adherent to a target form the “switchboard” that controls the target specificity of a neutrophil's mechanical response. These linkages are presumably actin-binding protein complexes associating with the cytoplasmic domains of cell-surface receptors that are engaged in adhesion to zymosan and Fc-domains. Recent micropipette experiments have provided a unique live view of “one-on-one” interactions between human neutrophils and their phagocytic targets. Our results revealed surprising differences between two prominent immunological pathways: the response to fungal targets (mimicked using zymosan particles), and antibody-mediated phagocytosis. Whereas antibody-coated targets were “pulled” into the cell in a straightforward manner, zymosan particles were internalized only after an initial outward “push”. We hypothesized that structural interactions between the cytoskeleton and the membrane patch adherent to a target play a pivotal role in the control of this target specificity. To verify and refine this hypothesis, we here compare our experimental results with predictions of suitable adaptations of a previously validated computational model of neutrophil mechanical behavior. By optimizing the model to best match our experiments, we corroborate that the primary mechanistic origin of the target-specific cell behavior indeed lies in the strength of cytoskeletal membrane anchors.
登录
查看更多内容
影响因子：
8.7
作者：
Goodridge HS;Wolf AJ;Underhill DM
通讯作者：
Underhill DM
影响因子：
56.9
作者：
DICARLO, FJ;FIORE, JV
通讯作者：
FIORE, JV
影响因子：
3.4
作者：
DEMBO, M;HARLOW, F
通讯作者：
HARLOW, F
巨噬细胞中涉及补体和FC受体介导的吞噬作用的不同细胞骨架结构的分子定义。
DOI：
10.1084/jem.184.2.627
发表时间：
1996-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allen LA;Aderem A
通讯作者：
Aderem A
影响因子：
4
作者：
Herant, Marc;Heinrich, Volkmar;Dembo, Micah
通讯作者：
Dembo, Micah