Department of Biomedical Engineering, Boston University, Boston, Massachusetts, United States of America.
PLoS Comput Biol. 2011 Jan 27;7(1):e1001068. doi: 10.1371/journal.pcbi.1001068.
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.
人中性粒细胞与酵母聚糖的相互作用会引发最初的突起细胞反应，这种反应与薄的薄片围绕抗体包被的靶标不同。最近的实验使我们假设这种行为的机制根源在于调节细胞膜和细胞骨架之间的相互作用。为了验证和完善这一假设，我们将实验结果与白细胞机械行为的计算机模型的预测进行了对比，并确定了该计算框架的最小机制变化集，该变化集再现了酵母聚糖和抗体吞噬作用之间的差异。我们证实，与附着在靶标上的膜片相连的细胞骨架的结构连接形成了“开关板”，控制着中性粒细胞机械反应的靶标特异性。这些连接可能是与参与与酵母聚糖和 Fc 结构域黏附的细胞表面受体的细胞质结构域结合的肌动蛋白结合蛋白复合物。
