肿瘤发展中的DNA转化、细胞表观遗传景观和开放复杂动力学

O. Naimark, Y. Bayandin, Y. Beloglazova, O. N. Gagarskich, V. Grishko, A. Nikitiuk, A. Voronina
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引用次数: 2

摘要

统计热力学允许在激发与碱基对之间氢键断裂相关的集体畸变模式(变性气泡)过程中,建立DNA转化的介观方法。将DNA模型(Peyrard-Bishop模型)的中间(非连续极限)与场描述(广义金兹堡-朗道方法)相结合,分析了与DNA系综中介观缺陷相关的集体开放复杂模式的动力学。集体模式动力学根据非平衡势(表观遗传景观)的统计预测形式描述了基因表达的不同情景,反映了具有中缺陷(开放复合物)的“软物质”的特定类型临界性-结构-尺度转变。非连续模型和连续模型热力学的主要区别在于与DNA呼吸相关的热波动相关的热化条件(具有呼吸动力学的局部激发)和由于开放复杂集体模式的产生而导致的失平衡势亚稳的spinodal分解的结构尺度参数。开放复杂集体模式具有开放复杂演化方程的自相似解(呼吸模式、自孤立模式和爆炸模式)的性质,可以解释定性的不同类型的潜在亚稳态。集体模式的子集代表了与不同表达动态情景相关的吸引子的相位变量,从而可以解释表观遗传景观的多稳定性和基因表达的黄图。在正常表达和肿瘤表达情景下,吸引子相空间显示出不同的表观遗传通路。这些情况得到了活的正常细胞和癌细胞的激光干涉显微镜的支持,说明了多分形和单分形动力学。
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DNA Transformation, Cell Epigenetic Landscape and Open Complex Dynamics in Cancer Development
Statistical thermodynamics allowed the formulation of mesoscopic approach of DNA transformation in course of the excitation of collective distortion modes (denaturation bubbles) associated with hydrogen bond breaking between the base pairs. Intermediate (non-continual limit) of DNA modeling (the Peyrard-Bishop model) is combined with the field description (generalized Ginzburg-Landau approach) to analyze the dynamics of collective open complex modes associated with mesodefects in the DNA ensemble. Collective modes dynamics describes different scenario of gene expression according to statistically predicted form of out-of-equilibrium potential (epigenetic landscape) reflecting specific type criticality of “soft matter” with mesodefects (open complexes) – the structural-scaling transition. Principal difference of thermodynamics of non-continual and continual models is thermalization conditions related to thermal fluctuations responsible for the DNA breathing (localized excitation with breather dynamics) and structural-scaling parameter responsible for spinodal decomposition of out-of-equilibrium potential metastability due to generation of open complex collective modes. Open complex collective modes have the nature of self-similar solutions (breathers, auto-solitary and blow-up modes) of open complex evolution equation accounting qualitative different types of potential metastabilities. Sub-sets of collective modes represent the phase variables of attractors associated with different scenario of expression dynamics, which allows the interpretation of multistability of the epigenetic landscape and the Huang diagram of gene expression. It was shown different epigenetic pathway in attractors phase space corresponding to normal and cancer expression scenario. These scenarios were supported by laser interference microscopy of living normal and cancer cells illustrating multi- and monofractal dynamics.
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来源期刊
Mathematical Biology and Bioinformatics
Mathematical Biology and Bioinformatics Mathematics-Applied Mathematics
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发文量
13
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