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Following the footprints of variability during filopodial growth
European Biophysics Journal ( IF 2.2 ) Pub Date : 2020-11-03 , DOI: 10.1007/s00249-020-01473-6
Daniela Senra 1 , Alejandra Páez 2, 3, 4 , Geraldine Gueron 2, 3 , Luciana Bruno 5 , Nara Guisoni 1
Affiliation  

Filopodia are actin-built finger-like dynamic structures that protrude from the cell cortex. These structures can sense the environment and play key roles in migration and cell–cell interactions. The growth-retraction cycle of filopodia is a complex process exquisitely regulated by intra- and extra-cellular cues, whose nature remains elusive. Filopodia present wide variation in length, lifetime and growth rate. Here, we investigate the features of filopodia patterns in fixed prostate tumor cells by confocal microscopy. Analysis of almost a thousand filopodia suggests the presence of two different populations: one characterized by a narrow distribution of lengths and the other with a much more variable pattern with very long filopodia. We explore a stochastic model of filopodial growth which takes into account diffusion and reactions involving actin and the regulatory proteins formin and capping, and retrograde flow. Interestingly, we found an inverse dependence between the filopodial length and the retrograde velocity. This result led us to propose that variations in the retrograde velocity could explain the experimental lengths observed for these tumor cells. In this sense, one population involves a wider range of retrograde velocities than the other population, and also includes low values of this velocity. It has been hypothesized that cells would be able to regulate retrograde flow as a mechanism to control filopodial length. Thus, we propound that the experimental filopodia pattern is the result of differential retrograde velocities originated from heterogeneous signaling due to cell–substrate interactions or prior cell–cell contacts.



中文翻译:

追踪丝状伪足生长过程中变异的足迹

丝状伪足是从细胞皮层突出的肌动蛋白构建的手指状动态结构。这些结构可以感知环境并在迁移和细胞间相互作用中发挥关键作用。丝状伪足的生长收缩周期是一个复杂的过程,受到细胞内和细胞外信号的精确调控,其性质仍然难以捉摸。丝状伪足在长度、寿命和生长速度方面存在很大差异。在这里,我们通过共聚焦显微镜研究固定前列腺肿瘤细胞中丝状伪足模式的特征。对近千种丝状伪足的分析表明存在两种不同的种群:一种特征是长度分布较窄,另一种具有非常长的丝状伪足的多变模式。我们探索了丝状伪足生长的随机模型,该模型考虑了涉及肌动蛋白和调节蛋白 formin 和 capping 的扩散和反应,以及逆行流。有趣的是,我们发现丝状足长度和逆行速度之间存在负相关。这一结果使我们提出逆行速度的变化可以解释对这些肿瘤细胞观察到的实验长度。从这个意义上说,一个群体比另一个群体涉及更广泛的逆行速度,并且还包括该速度的低值。已经假设细胞将能够调节逆行流动作为控制丝状体长度的机制。因此,

更新日期:2020-11-03
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