Collective Migration of Loosely Connected Cell Clusters

细胞运动是一种受到严格调控的行为，在几个生物过程中起着至关重要的作用。它对组织形成、伤口愈合和免疫反应都很重要。运动细胞的异常行为可能导致严重的疾病，包括血管疾病和癌症转移。因此，理解和控制控制细胞迁移的机制是有用的。单细胞的迁移已被广泛研究。众所周知，这种迁移可能是自发的，也可能是受外部线索的引导。然而，我们对多个细胞协调运动的理解仍然有限。该奖项将支持基础理论和计算研究，以研究松散连接的细胞簇的集体运动。具体来说，通过生化和机械信号同时进行的细胞相互作用将被观察到。这种类型的集体运动被认为密切调节早期胚胎发生和癌症转移。因此，该项目的成果将推进我们对集体细胞迁移的科学知识，并对国家健康和繁荣产生持续影响。大多数关于细胞集体迁移的研究都集中在上皮细胞紧密堆积的单层的协调运动上。通过机械和化学相互作用进行交流的松散连接的细胞团的集体迁移很少受到关注，部分原因是紧密排列的细胞团的计算方法不适用于机械和生化相互作用的松散细胞团。我们研究了一种独特而可行的计算方法来研究这个问题。这项研究将对集体细胞迁移领域产生变革性的影响，但除此之外，该项目还将提供一个通用的计算框架，可用于研究生物医学工程一般领域未来工作中的其他问题。这个计算框架最终可以对伤口愈合、免疫反应和转移产生新的见解。该计算框架也有望在其他工程领域产生影响，如流固耦合、多孔介质流动的孔隙尺度建模和增材制造。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Cellular motion is a tightly regulated action that plays a crucial role in several biological processes. It is important to tissue formation, wound healing, and immune response. Abnormal behavior of motile cells may lead to serious conditions, including vascular disease and cancer metastasis. Therefore, understanding and controlling the mechanisms that control cell migration is useful. The migration of single cells has been profusely studied. It is known that this migration may be spontaneous or guided by external cues. However, our understanding of the coordinated motion of multiple cells remains limited. This award will support fundamental theoretical and computational research to study the collective motion of loosely connected cell clusters. Specifically, cell interaction through simultaneous biochemical and mechanical signals simultaneously will be observed. This type of collective motion is known to tightly regulate early embryogenesis and cancer metastasis. Therefore, the results of this project will advance our scientific knowledge on collective cell migration, and also have a sustained impact on national health and prosperity.Most research on collective cell migration has focused on the coordinated motion of tightly-packed monolayers of epithelial cells. The collective migration of loosely connected cell clusters that communicate via mechanical and chemical interactions has received little attention partially because the computational methods for tightly-packed collectives are not applicable to loose clusters that interact mechanically and biochemically. We researched a unique and enabling computational method to study this problem. The research will have a transformative impact in the field of collective cell migration, but in addition, the project will also deliver a general computational framework that can be used to study other problems in future work in the general area of biomedical engineering. This computational framework could ultimately yield new insights into wound healing, immune response, and metastasis. The computational framework is also expected to have impact in other fields of engineering such as fluid-structure interaction, pore-scale modeling of porous media flow, and additive manufacturing.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.