Performance of a population of independent filaments in lamellipodial protrusion
Performance of a population of independent filaments in lamellipodial protrusion
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DOI：
10.1529/biophysj.107.125005
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发表时间：
2008-08-01
影响因子：
3.4
通讯作者：
Borisy, Gary G.
中科院分区：
文献类型：
--
作者：
Schaus, Thomas E.;Borisy, Gary G.
肌动蛋白聚合负责移动各种各样的负载，从免疫细胞、癌症细胞和其他运动细胞的膜结合的丝足和片脂的突起，到一些细胞内病原体的推进。对这些系统产生的力和速度的普遍解释因缺乏对一群独立细丝如何推动这些载荷的理解而受到阻碍。支撑膜负载的细丝突起片状基团被认为是由布朗棘轮机制操作的，总体组织由树枝形核/阵列-踏板模型支配。我们将这两个模型结合到一个二维的随机计算机模型中，研究在不同的假设下力和速度的产生是如何变化的。性能对细丝群体内的各个聚合事件之间分担突出功的程度非常敏感。有三种机制促进了这种“工作共享”：1)，大多数系统，包括LIMELLIFIDIA，都利用细丝负载距离的自组织分布，这有助于减小单体的有效尺寸并显著提高性能。2)，柔性膜允许在宽前沿上保持一致的性能。3)最后，非常灵活的细丝能够非常均匀地分担功，因此具有近乎完美的理论性能。然而，片状脂膜的短暂拴系限制了它们的效果，并要求最小的细丝硬度。总体而言，我们估计片状脂膜与40纳米弯曲长度的细丝和低特征系缆力一起工作。模拟的片状脂膜呈现出S形的力-速度关系，并且只在细丝之间适度地很好地分担突出功，大约以理论力和速度最大值的一半执行。在这种工作共享水平上，天然单体的大小对于生成速度是最佳的。
Actin polymerization is responsible for moving a wide variety of loads, from the protrusion of membrane-bound filopodia and lamellipodia of immune, cancer, and other motile cells, to the propulsion of some intracellular pathogens. A universal explanation of the forces and velocities generated by these systems has been hampered by a lack of understanding in how a population of independent filaments pushes these loads. Protrusion of a lamellipodium by the very filaments supporting the membrane load is thought to operate by the Brownian ratchet mechanism, with overall organization governed by the dendritic-nucleation/array-treadmilling model. We have incorporated these two models into a two-dimensional, stochastic computer model of lamellipodial protrusion, and studied how force and velocity generation varied under different assumptions. Performance is very sensitive to the extent to which the work of protrusion is shared among individual polymerization events within the filament population. Three identified mechanisms promote this "work-sharing": 1), Most systems, including lamellipodia, utilize a self-organizing distribution of filament-load distances which serves to decrease the effective size of a monomer and dramatically improve performance. 2), A flexible membrane allows for consistent performance over wide leading edges. 3), Finally, very flexible filaments are capable of sharing work very uniformly, and therefore, of near-perfect theoretical performance. Transient tethering to the lamellipodial membrane limits their efficacy, however, and mandates a minimum filament stiffness. Overall, we estimate lamellipodia to operate with 40-nm bending-length filaments and low characteristic tether forces. Modeled lamellipodia exhibit sigmoidal force-velocity relationships and share the work of protrusion only moderately well among filaments, performing at approximately one-half of theoretical force and velocity maximums. At this level of work-sharing, the natural monomer size is optimal for generating velocity.