کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2035594 | 1072199 | 2012 | 13 صفحه PDF | دانلود رایگان |
SummaryHow cells form global, self-organized structures using genetically encoded molecular rules remains elusive. Here, we take a synthetic biology approach to investigate the design principles governing cell polarization. First, using a coarse-grained computational model, we searched for all possible simple networks that can achieve polarization. All solutions contained one of three minimal motifs: positive feedback, mutual inhibition, or inhibitor with positive feedback. These minimal motifs alone could achieve polarization under limited conditions; circuits that combined two or more of these motifs were significantly more robust. With these design principles as a blueprint, we experimentally constructed artificial polarization networks in yeast, using a toolkit of chimeric signaling proteins that spatially direct the synthesis and degradation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3). Circuits with combinatorial motifs yielded clear foci of synthetic PIP3 that can persist for nearly an hour. Thus, by harnessing localization-regulated signaling molecules, we can engineer simple molecular circuits that reliably execute spatial self-organized programs.
Graphical AbstractFigure optionsDownload high-quality image (299 K)Download as PowerPoint slideHighlights
► Computational model identified three minimal network motifs for cell polarization
► Combining minimal motifs increased robustness of polarization to parameter variation
► PIP3 polarization networks were designed using engineered chimeric signaling proteins
► Synthetic networks combining minimal motifs yield strong, sustained PIP3 poles
Journal: - Volume 151, Issue 2, 12 October 2012, Pages 320–332