Czirok Andras, Isai Dona Greta
Department of Anatomy & Cell Biology, University of Kansas Medical Center, Kansas City, KS, USA. Department of Biological Physics, Eotvos University, Budapest, Hungary.
Phys Biol. 2014 Dec 15;12(1):016005. doi: 10.1088/1478-3975/12/1/016005.
We propose a three-dimensional mechanical model of embryonic tissue dynamics. Mechanically coupled adherent cells are represented as particles interconnected with elastic beams which can exert non-central forces and torques. Tissue plasticity is modeled by a stochastic process consisting of a connectivity change (addition or removal of a single link) followed by a complete relaxation to mechanical equilibrium. In particular, we assume that (i) two non-connected, but adjacent particles can form a new link; and (ii) the lifetime of links is reduced by tensile forces. We demonstrate that the proposed model yields a realistic macroscopic elasto-plastic behavior and we establish how microscopic model parameters determine material properties at the macroscopic scale. Based on these results, microscopic parameter values can be inferred from tissue thickness, macroscopic elastic modulus and the magnitude and dynamics of intercellular adhesion forces. In addition to their mechanical role, model particles can also act as simulation agents and actively modulate their connectivity according to specific rules. As an example, anisotropic link insertion and removal probabilities can give rise to local cell intercalation and large scale convergent extension movements. The proposed stochastic simulation of cell activities yields fluctuating tissue movements which exhibit the same autocorrelation properties as empirical data from avian embryos.
我们提出了一个胚胎组织动力学的三维力学模型。机械耦合的贴壁细胞被表示为通过弹性梁相互连接的粒子,这些弹性梁可以施加非中心力和扭矩。组织可塑性通过一个随机过程来建模,该过程包括连接性变化(单个连接的添加或去除),随后完全松弛到力学平衡。具体而言,我们假设:(i)两个未连接但相邻的粒子可以形成一个新的连接;(ii)连接的寿命会因拉力而缩短。我们证明所提出的模型产生了现实的宏观弹塑性行为,并确定了微观模型参数如何在宏观尺度上决定材料特性。基于这些结果,可以从组织厚度、宏观弹性模量以及细胞间粘附力的大小和动力学推断微观参数值。除了其力学作用外,模型粒子还可以充当模拟主体,并根据特定规则主动调节其连接性。例如,各向异性的连接插入和去除概率会导致局部细胞插入和大规模的汇聚延伸运动。所提出的细胞活动随机模拟产生了波动的组织运动,这些运动表现出与来自鸟类胚胎的经验数据相同的自相关特性。