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首页> 外文期刊>Journal of Theoretical Biology >A multi-scale, discrete-cell simulation of organogenesis: Application to the effects of strain stimulus on collective cell behavior during ameloblast migration.
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A multi-scale, discrete-cell simulation of organogenesis: Application to the effects of strain stimulus on collective cell behavior during ameloblast migration.

机译：器官发生的多尺度，离散细胞模拟：应用于应变刺激对成釉细胞迁移过程中集体细胞行为的影响。

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摘要

A multi-scale strategy is presented for simulating organogenesis that uses a single cell response function to define the behavior of individual cells in an organ-scale simulation of a large cell population. The response function summarizes detailed information about the behavior of individual cells in a sufficiently economical way that the organ-scale model can be commensurate with the entire organ. The first application demonstrates the effects of strain stimulus on the migration of ameloblasts during enamel formation. Ameloblasts are an attractive study case because mineralization preserves a complete record of their migratory paths. The response function in this case specifies the motions of cells responding to strain stimuli that propagate through the population. The strain stimuli are related to the curvature of the surface from which the ameloblasts migrate (the dentin-enamel junction or DEJ). A single unknown rate parameter is calibrated by an independent datum from the human tooth. With no remaining adjustable parameters, the theory correctly predicts aspects of the fracture-resistant, wavy microstructure of enamel in the human molar, including wavelength variations and the rate of wave amplitude damping. At a critical value of curvature of the DEJ, a transition in the ordering of cells occurs, from invariant order over the whole population to self-assembly of the population into groups or gangs. The prediction of an ordering transition and the predicted critical curvature are consistent with gnarled enamel in the cusps of the human molar. The calibration of the model using human data also predicts waves in the mouse incisor and an ordering transition at the chimpanzee cingulum. Widespread compressive strain is predicted late in the migration for both the human molar and mouse incisor, providing a possible signal for the termination of amelogenesis.
机译：提出了用于模拟器官发生的多尺度策略，该策略使用单个细胞响应功能来定义大细胞群体的器官尺度模拟中单个细胞的行为。响应函数以足够经济的方式总结了有关单个细胞行为的详细信息，以使器官规模模型可以与整个器官相称。第一个应用证明了应变刺激对釉质形成过程中成釉细胞迁移的影响。成釉细胞是一个有吸引力的研究案例，因为矿化作用保留了其迁移路径的完整记录。在这种情况下，响应函数指定了响应通过种群传播的应变刺激的细胞的运动。应变刺激与成釉细胞迁移的表面曲率（牙本质-牙釉质结或DEJ）有关。单个未知速率参数由来自人类牙齿的独立数据校准。在没有剩余可调整参数的情况下，该理论正确地预测了人类磨牙牙釉质的抗断裂，波浪状微观结构的各个方面，包括波长变化和波幅衰减率。在DEJ曲率的临界值处，发生了细胞顺序的过渡，从整个种群的不变顺序到种群自组装成组或团伙的自组装。有序过渡的预测和预测的临界曲率与人类磨牙尖处粗糙的搪瓷相一致。使用人类数据对模型进行的校准还可以预测小鼠门齿中的波以及黑猩猩扣带的有序转移。预计在人类磨牙和小鼠门齿的迁移后期会出现广泛的压缩应变，为终止牙釉质形成提供了可能的信号。

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