标题： 组织中由于细胞尺度和宏观尺度力之间的反馈而导致自组织的微观生物物理模型 显示英文标题

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

摘要： 我们开发了一个微观生物物理模型，用于研究人工组织的自组织和重塑，该模型由细胞与细胞外基质（ECM）之间的微观主动力以及组织内部产生的宏观力共同驱动，并与实验结果高度一致。 微观主动力是由细胞与ECM之间在$\mu$米尺度上的相互作用所激发的，当大量细胞共同作用时，这些力会驱动并受到宏观尺度上的组织自组织和重塑的反馈循环影响。 为了理解这一循环，有必要：(1) 构建能够模拟组织中大量细胞的微观生物物理模型；(2) 将这些模型与实验数据进行验证和校准；以及(3) 理解细胞与细胞外基质之间的主动反馈及其与组织宏观自组织和重塑的关系。 我们的微观生物物理模型包括一个代表ECM的收缩网络，该网络通过偶极子力与大量细胞相互作用，以描述组织的宏观自组织和重塑。 我们使用模拟退火方法求解该模型，发现与人工神经组织实验结果高度一致。 我们讨论了模型参数的校准问题。 我们得出结论，微观细胞-ECM偶极子相互作用与组织尺度力之间的反馈是驱动组织宏观自组织和重塑的关键因素。 我们讨论了该生物物理模型在人工组织模拟和合理设计中的应用。 显示英文摘要

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 $\mu$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.