Department of Cell Biochemistry, University of Groningen, Groningen, The Netherlands.
Biophys J. 2010 Nov 17;99(10):3345-54. doi: 10.1016/j.bpj.2010.09.042.
Many amoeboid cells move by extending pseudopods. Here I present a new stochastic model for chemotaxis that is based on pseudopod extensions by Dictyostelium cells. In the absence of external cues, pseudopod extension is highly ordered with two types of pseudopods: de novo formation of a pseudopod at the cell body in random directions, and alternating right/left splitting of an existing pseudopod that leads to a persistent zig-zag trajectory. We measured the directional probabilities of the extension of splitting and de novo pseudopods in chemoattractant gradients with different steepness. Very shallow cAMP gradients can bias the direction of splitting pseudopods, but the bias is not perfect. Orientation of de novo pseudopods require much steeper cAMP gradients and can be more precise. These measured probabilities of pseudopod directions were used to obtain an analytical model for chemotaxis of cell populations. Measured chemotaxis of wild-type cells and mutants with specific defects in these stochastic pseudopod properties are similar to predictions of the model. These results show that combining splitting and de novo pseudopods is a very effective way for cells to obtain very high sensitivity to stable gradient and still be responsive to changes in the direction of the gradient.
许多变形虫细胞通过延伸伪足来移动。在这里，我提出了一种新的基于变形虫细胞伪足延伸的趋化性随机模型。在没有外部线索的情况下，伪足延伸具有高度的有序性，存在两种类型的伪足：在随机方向上在细胞体处新形成的伪足，以及现有伪足的交替向右/向左分裂，导致持续的之字形轨迹。我们测量了在不同陡度的趋化因子梯度中分裂和新形成的伪足延伸的方向概率。非常浅的 cAMP 梯度可以使分裂伪足的方向产生偏差，但偏差并不完美。新形成的伪足的定向需要更陡的 cAMP 梯度，并且可以更精确。这些测量的伪足方向概率用于获得细胞群体趋化性的分析模型。对具有这些随机伪足特性特定缺陷的野生型细胞和突变体的测量趋化性与模型的预测相似。这些结果表明，结合分裂和新形成的伪足是细胞获得对稳定梯度的高灵敏度并仍然对梯度方向的变化做出响应的非常有效的方法。
