Chemotaxis overrides Barotaxis during Directional Decision-Making in Dictyostelium discoideum
Chemotaxis overrides Barotaxis during Directional Decision-Making in Dictyostelium discoideum
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DOI：
10.1101/2020.01.14.904748
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发表时间：
2020-01
期刊：
影响因子：
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通讯作者：
Y. Belotti;D. Mcgloin;C. Weijer
中科院分区：
文献类型：
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作者：
Y. Belotti;D. Mcgloin;C. Weijer
中性粒细胞和树突状细胞，除了它们特有的趋化运动反应外，还被证明能够检测并对局部水力阻力的差异(正压)做出反应。此外，对于中性粒细胞，已经提出了压力趋化优先于趋化。在这里，我们使用一个不对称的分叉微通道来研究Dictyostelius细胞是否也对水力阻力或主要对化学梯度做出反应。这种通道设计允许我们将水力和化学刺激分离，通过提供向上移动化学梯度或向下移动化学梯度进入水力阻力低100倍的通道之间的选择。在这种情况下，趋化作用总是高于压力趋化作用。观察到面临微通道分叉的细胞通常会部分分裂其前沿，并开始向两个通道移动。细胞在更陡峭的阵营梯度中移动得更快，更容易分裂。当伪足沿cAMP梯度向上移动的平均速度比伪足向下移动的平均速度高20%时，就做出了收回伪足离开cAMP源的决定。令人惊讶的是，这一决定门槛与营地坡度和移动速度无关。它表明，一个临界力失衡阈值是重新极化决定的基础。意义陈述我们研究盘基网柄菌细胞在含有不对称分叉的工程微通道内迁移的方向性“决策”。与中性粒细胞和未成熟的树突状细胞不同，Dictyostelials细胞强烈优先于化学物质而不是正压引导性信号。在更陡峭的阵营梯度中的细胞以更快的速度迁移，当遇到通道中的分叉时，更容易分裂它们的前沿。当两个相互竞争的伪足之间的临界张力梯度被超过时，就会决定收回指向不利方向的伪足。这些实验表明，尽管气压趋势性不是主要的指导信号，但细胞力学在前沿动力学中发挥着重要作用，包括前沿分裂、极化和回缩。
Neutrophils and dendritic cells have, besides their well characterised chemotactic movement responses, been shown to be able to detect and respond to local differences in hydraulic resistance (barotaxis). Furthermore, for neutrophils, it has been suggested that barotaxis overrides chemotaxis. Here, we investigate whether Dictyostelium cells also respond to hydraulic resistance or primarily to chemical gradients using an asymmetric bifurcating micro-channel. This channel design allows us to decouple hydraulic and chemical stimuli, by providing a choice between moving up a chemical gradient or down a chemical gradient into a channel with 100 times lower hydraulic resistance. Under these conditions chemotaxis always overrides barotaxis. Cells confronted by a microchannel bifurcation are observed to often partially split their leading edge and to start moving into both channels. Cells in steeper cAMP gradients, that move faster, split more readily. The decision to retract the pseudopod moving away from the cAMP source is made when the average velocity of the pseudopod moving up the cAMP gradient is 20% higher than the average velocity of the pseudopod moving down the gradient. Surprisingly, this decision threshold is independent of the steepness of the cAMP gradient and speed of movement. It indicates that a critical force imbalance threshold underlies the repolarisation decision. Significance Statement We investigate the directional ‘decision-making’ of Dictyostelium discoideum cells migrating within engineered micro-channels harbouring asymmetric bifurcations. Unlike neutrophils and immature dendritic cells, Dictyostelium cells strongly prioritise chemical over barotactic guidance cues. Cells in steeper cAMP gradients migrate at higher speeds, split their leading edges more readily when confronted with a bifurcation in the channel. The decision to retract a pseudopod pointing in an unfavourable direction occurs when a critical tension gradient between two competing pseudopods is surpassed. These experiments show that although barotaxis is not a major guidance cue, cellular mechanics plays a major role in leading edge dynamics, including front splitting and polarisation and retraction.