3D Cell Aggregates Amplify Diffusion Signals

3D Cell Aggregates Amplify Diffusion Signals
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3D 细胞聚集体放大扩散信号

DOI:
10.1101/2023.06.28.546952
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发表时间:
2023
期刊:
--
影响因子:
--
通讯作者:
Arjmandi H
Arjmandi H
中科院分区:
--
文献类型:
--
作者:
Arjmandi H

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生物物理模型可以预测包括3D细胞培养物(3DCC)在内的细胞培养物的行为,从而减少对昂贵且耗时的实验的需求。具体而言,质量传递模型使得能够研究3DCC中营养物质、氧气、信号分子和药物的运输,这需要定义3DCC和周围介质之间的边界条件(BC)。然而,准确地建模的BC,涉及的内部和外部边界之间的边界处的3DCC和介质的浓度,仍然是一个挑战,本文使用理论和实验方法解决。所提供的生物物理分析表明,内边界处的分子浓度高于外边界处的分子浓度,揭示了放大因子,这通过基于粒子的模拟器(PBS)得到证实。由于扩增因子,PBS证实当将具有低浓度靶分子的3DCC引入具有较高浓度的培养基时,培养基中的分子浓度迅速降低。实验中以肝脏球状体为3DCC,葡萄糖为靶分子。PBS被利用来设计这些实验,并且结果与我们提出的理论和导出的性质一致,特别是当具有更高的介质体积时。
Biophysical models can predict the behavior of cell cultures including 3D cell cultures (3DCCs), thereby reducing the need for costly and time-consuming experiments. Specifically, mass transfer models enable studying the transport of nutrients, oxygen, signaling molecules, and drugs in 3DCC which requires defining boundary conditions (BC) between the 3DCC and surrounding medium. However, accurately modeling the BC that relates the inner and outer boundary concentrations at the border between the 3DCC and the medium, remains a challenge that this paper addresses using both theoretical and experimental methods. The provided biophysical analysis indicates that the concentration of molecules at the inner boundary is higher than that at the outer boundary, revealing an amplification factor, which is confirmed by a particle-based simulator (PBS). Due to the amplification factor, the PBS confirms that when a 3DCC with a low concentration of target molecules is introduced to a culture medium with a higher concentration, the molecule concentration in the medium rapidly decreases. Liver spheroids are used as the 3DCC and glucose as the target molecule in the experiments. The PBS is leveraged to design these experiments, and results agree with our proposed theory and derived properties, particularly when having a higher medium volume.
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