Engineering biological structures of prescribed shape using self-assembling multicellular systems
Engineering biological structures of prescribed shape using self-assembling multicellular systems
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DOI：
10.1073/pnas.0400164101
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发表时间：
2004-03-02
影响因子：
11.1
通讯作者：
Forgacs, G
中科院分区：
文献类型：
--
作者：
Jakab, K;Neagu, A;Forgacs, G
自我组装是在无生命和有生命的系统中驱动结构组织的基本过程。正是在早期发育的细胞和组织的自我组装过程中，有机体及其部分最终形成了它们的最终形状。尽管通过自组装的发育模式是在严格的基因控制下进行的，但很明显，最终是物理机制导致了复杂的结构。在这里，我们展示了，通过实验和计算机模拟，组织流动性如何可以用来在体外构建指定几何形状的组织结构。含有数千个细胞的球形聚集体因组织流动性而形成，被连续植入圆形形状的生物相容水凝胶中。根据凝胶的性质，在孵化时，聚集体要么融合成环形3D结构，要么其组成细胞分散到周围的基质中。模型模拟再现了实验观察到的形状，表明结构演化的控制参数是凝聚体-凝胶界面张力。基于模型的分析还表明，观察到的环形结构代表了细胞系统的亚稳态，其寿命取决于细胞-细胞和细胞-基质相互作用的大小。因此，这些构造物可以长期存在。我们认为，由器官特异性细胞组成的球形聚集体可以作为器官打印进化技术中的“生物墨水”。
Self-assembly is a fundamental process that drives structural organization in both inanimate and living systems. It is in the course of self-assembly of cells and tissues in early development that the organism and its parts eventually acquire their final shape. Even though developmental patterning through self-assembly is under strict genetic control it is clear that ultimately it is physical mechanisms that bring about the complex structures. Here we show, both experimentally and by using computer simulations, how tissue liquidity can be used to build tissue constructs of prescribed geometry in vitro. Spherical aggregates containing many thousands of cells, which form because of tissue liquidity, were implanted contiguously into biocompatible hydrogels in circular geometry. Depending on the properties of the gel, upon incubation, the aggregates either fused into a toroidal 3D structure or their constituent cells dispersed into the surrounding matrix. The model simulations, which reproduced the experimentally observed shapes, indicate that the control parameter of structure evolution is the aggregate-gel interfacial tension. The model-based analysis also revealed that the observed toroidal structure represents a metastable state of the cellular system, whose lifetime depends on the magnitude of cell-cell and cell-matrix interactions. Thus, these constructs can be made long-lived. We suggest that spherical aggregates composed of organ-specific cells may be used as "bio-ink" in the evolving technology of organ printing.