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Following the footprints of variability during filopodia growth
bioRxiv - Biophysics Pub Date : 2020-10-23 , DOI: 10.1101/2020.10.22.349084
Daniela Senra , Alejandra Páez , Geraldine Gueron , Luciana Bruno , Nara Guisoni

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 cancer 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 filopodia 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 filopodia 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:

追踪丝虫足生长过程中的变异性足迹

丝足是肌动蛋白构建的手指状动态结构,从细胞皮质突出。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调节,其本质仍然难以捉摸。丝足虫在长度,寿命和生长率方面存在很大差异。在这里,我们通过共聚焦显微镜研究固定前列腺癌细胞中丝状伪足的特征。对近一千种丝虫足的分析表明存在两种不同的种群:一种特征是长度分布狭窄,另一种具有非常长的丝虫足的变化模式。我们探讨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和加帽以及逆行流动的扩散和反应。有趣的是,我们发现了前肢长度与逆行速度之间的反比关系。这一结果使我们提出,逆行速度的变化可以解释观察到的这些肿瘤细胞的实验长度。从这个意义上讲,一个种群所涉及的逆行速度范围比另一种群要大,并且该速度值也较低。已经假设细胞能够调节逆行血流作为控制丝状伪足长度的机制。从而,
更新日期:2020-10-26
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