Filopodial retraction force is generated by cortical actin dynamics and controlled by reversible tethering at the tip
Filopodial retraction force is generated by cortical actin dynamics and controlled by reversible tethering at the tip
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DOI：
10.1073/pnas.1316572110
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发表时间：
2013-11-19
影响因子：
11.1
通讯作者：
Bassereau, Patricia
中科院分区：
文献类型：
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作者：
Bornschloegl, Thomas;Romero, Stephane;Bassereau, Patricia
丝状伪足是动态的、手指状的质膜突起，可以感知细胞的机械和化学环境。在这里，我们在上皮细胞中表明，丝状基座伸展和收缩的动力学是由顶端的肌动蛋白聚合速率和丝状基座底部的逆行流动之间的差异决定的。珠子附着到丝状末端，局部减少了肌动蛋白的聚合，并通过逆流导致收缩，这让人想起病原体入侵细胞的过程。使用光钳，我们证明了丝径向回缩以恒定的速度发生，抵抗力高达50pN。我们的测量结果表明，皮质中的逆行血流以及丝状肌动蛋白网络和皮质肌动蛋白网络之间的摩擦耦合是丝状伪足的主要回缩力发生器。然而，肌动蛋白细丝和顶端的膜之间的连接限制了丝径缩回所施加的力。在顶端连接机械断裂时，丝状足通过其质膜施加15pN的被动回缩力。顶端的瞬时重新连接允许丝状支架在明确定义的力范围内以加载和失败的方式连续探测周围环境。
Filopodia are dynamic, finger-like plasma membrane protrusions that sense the mechanical and chemical surroundings of the cell. Here, we show in epithelial cells that the dynamics of filopodial extension and retraction are determined by the difference between the actin polymerization rate at the tip and the retrograde flow at the base of the filopodium. Adhesion of a bead to the filopodial tip locally reduces actin polymerization and leads to retraction via retrograde flow, reminiscent of a process used by pathogens to invade cells. Using optical tweezers, we show that filopodial retraction occurs at a constant speed against counteracting forces up to 50 pN. Our measurements point toward retrograde flow in the cortex together with frictional coupling between the filopodial and cortical actin networks as the main retraction-force generator for filopodia. The force exerted by filopodial retraction, however, is limited by the connection between filopodial actin filaments and the membrane at the tip. Upon mechanical rupture of the tip connection, filopodia exert a passive retraction force of 15 pN via their plasma membrane. Transient reconnection at the tip allows filopodia to continuously probe their surroundings in a load-and-fail manner within a well-defined force range.