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arXiv 1902.02768physics.bio-phcond-mat.softcond-mat.stat-mech
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由于细胞和宏观尺度力之间的反馈,组织中自组织的微观生物物理模型

Microscopic biophysical model of self-organization in tissue due to feedback between cell- and macroscopic-scale forces

J. P. Hague, P. W. Mieczkowski, C. O'Rourke, A. J. Loughlin, J. B. Phillips

摘要:

我们开发了一个微观生物物理模型的自组织和重塑的人工组织,这是共同驱动的细胞和细胞外基质(ECM)之间的微观主动力,和宏观力量,在组织内发展,发现与实验密切一致。微观主动力由细胞和它们存在于其中的ECM之间的$μ$ m尺度相互作用刺激,并且当大量细胞一起作用时,这些力驱动宏观尺度自组织和反馈回路中的组织重塑,并且受到宏观尺度自组织和反馈回路中的组织重塑的影响。为了理解这个循环,需要:(1)构建微观生物物理模型,可以模拟组织中发现的大量细胞的这些过程;(2)根据实验数据验证和校准这些模型;(3)理解细胞和细胞外基质之间的主动反馈,以及它与宏观自组织和组织重塑的关系。我们的微观生物物理模型由代表ECM的收缩网络组成,其通过偶极力与大量细胞相互作用,以描述组织的宏观自组织和重塑。我们使用模拟退火来解决模型,发现与人工神经组织的实验密切一致。我们讨论了模型参数的标定。我们的结论是微观细胞-ECM偶极相互作用和组织尺度力之间的反馈,是驱动宏观自组织和重塑组织的关键因素。讨论了生物物理模型在人工组织模拟和合理设计中的应用。

英文摘要:

We develop a microscopic biophysical model for self-organization and reshaping of artificial tissue, that is co-driven by microscopic active forces between cells and extracellular matrix (ECM), and macroscopic forces that develop within the tissue, finding close agreement with experiment. Microscopic active forces are stimulated by $μ$m scale interactions between cells and the ECM within which they exist, and when large numbers of cells act together these forces drive, and are affected by, macroscopic-scale self-organization and reshaping of tissues in a feedback loop. To understand this loop, there is a need to: (1) construct microscopic biophysical models that can simulate these processes for the very large number of cells found in tissues; (2) validate and calibrate those models against experimental data; and (3) understand the active feedback between cells and the extracellular matrix, and its relationship to macroscopic self-organization and reshaping of tissue. Our microscopic biophysical model consists of a contractile network representing the ECM, that interacts with a large number of cells via dipole forces, to describe macroscopic self-organization and reshaping of tissue. We solve the model using simulated annealing, finding close agreement with experiments on artificial neural tissue. We discuss calibration of model parameters. We conclude that feedback between microscopic cell-ECM dipole interactions and tissue-scale forces, is a key factor in driving macroscopic self-organization and reshaping of tissue. We discuss application of the biophysical model to simulation and rational design of artificial tissues.

机构、总结、中文摘要均由AI分析而来,可能存在错误,请以论文正文为准。

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