Muzzio N E, Pasquale M A, Huergo M A C, Bolzán A E, González P H, Arvia A J
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Universidad Nacional de La Plata (UNLP), CONICET, Sucursal 4, Casilla de Correo 16, 1900, La Plata, Argentina.
Cátedra de Patología, Facultad de Ciencias Médicas, UNLP, CIC, Calle 60 y 120, 1900, La Plata, Bs. As., Argentina.
J Biol Phys. 2016 Jun;42(3):477-502. doi: 10.1007/s10867-016-9418-3. Epub 2016 Jun 7.
To deal with complex systems, microscopic and global approaches become of particular interest. Our previous results from the dynamics of large cell colonies indicated that their 2D front roughness dynamics is compatible with the standard Kardar-Parisi-Zhang (KPZ) or the quenched KPZ equations either in plain or methylcellulose (MC)-containing gel culture media, respectively. In both cases, the influence of a non-uniform distribution of the colony constituents was significant. These results encouraged us to investigate the overall dynamics of those systems considering the morphology and size, the duplication rate, and the motility of single cells. For this purpose, colonies with different cell populations (N) exhibiting quasi-circular and quasi-linear growth fronts in plain and MC-containing culture media are investigated. For small N, the average radial front velocity and its change with time depend on MC concentration. MC in the medium interferes with cell mitosis, contributes to the local enlargement of cells, and increases the distribution of spatio-temporal cell density heterogeneities. Colony spreading in MC-containing media proceeds under two main quenching effects, I and II; the former mainly depending on the culture medium composition and structure and the latter caused by the distribution of enlarged local cell domains. For large N, colony spreading occurs at constant velocity. The characteristics of cell motility, assessed by measuring their trajectories and the corresponding velocity field, reflect the effect of enlarged, slow-moving cells and the structure of the medium. Local average cell size distribution and individual cell motility data from plain and MC-containing media are qualitatively consistent with the predictions of both the extended cellular Potts models and the observed transition of the front roughness dynamics from a standard KPZ to a quenched KPZ. In this case, quenching effects I and II cooperate and give rise to the quenched-KPZ equation. Seemingly, these results show a possible way of linking the cellular Potts models and the 2D colony front roughness dynamics.
为了处理复杂系统,微观和全局方法变得特别受关注。我们之前关于大细胞集落动力学的结果表明,它们的二维前沿粗糙度动力学分别在普通或含甲基纤维素(MC)的凝胶培养基中与标准的 Kardar-Parisi-Zhang(KPZ)方程或淬火 KPZ 方程兼容。在这两种情况下,集落成分的非均匀分布的影响都很显著。这些结果促使我们考虑单细胞的形态和大小、复制率以及运动性来研究这些系统的整体动力学。为此,研究了在普通和含 MC 的培养基中具有不同细胞数量(N)且呈现准圆形和准线性生长前沿的集落。对于小 N,平均径向前沿速度及其随时间的变化取决于 MC 浓度。培养基中的 MC 干扰细胞有丝分裂,导致细胞局部增大,并增加时空细胞密度异质性的分布。在含 MC 的培养基中集落扩展在两种主要的淬火效应 I 和 II 下进行;前者主要取决于培养基的组成和结构,后者由局部增大的细胞区域的分布引起。对于大 N,集落以恒定速度扩展。通过测量细胞轨迹和相应的速度场来评估的细胞运动性特征,反映了增大的、移动缓慢的细胞的影响以及培养基的结构。来自普通和含 MC 培养基的局部平均细胞大小分布和单个细胞运动性数据在质量上与扩展细胞 Potts 模型的预测以及观察到的前沿粗糙度动力学从标准 KPZ 到淬火 KPZ 的转变一致。在这种情况下,淬火效应 I 和 II 协同作用并产生淬火 KPZ 方程。显然,这些结果展示了一种将细胞 Potts 模型与二维集落前沿粗糙度动力学联系起来的可能方式。