细胞群体极化、排列和迁移行为的理论建模和实验研究

Collective behaviors of multiple cells are complex phenomena that are based on the coordination of interaction and information change among the cells. These collective cell behaviors play critical roles in many fundamental processes, including not only physiological processes, but also pathological processes, such as morphogenesis, wound healing, and cancer metastasis. Recent experiments showed that the mechanical stimuli, such as external force, properties of cell micro-environment, and cell-cell interaction, could regulate the behaviors of the collective cell polarization, alignment and migration. Currently, the mechanisms in the regulation are still highly unclear, and there are many basic scientific questions remain to be solved. To address these scientific problems, we proposed to use an approach of combination of experimental studies and multiscale modeling to study the behaviors of collective cell polarization, alignment and migration. We aim to find the main parameters that control the collective behaviors of multiple cells, and then build the quantitative relation between the mechanical stimuli and cell behaviors, and thus try to find the underlying mechanisms of regulation of the collective cell polarization, alignment and migration under the application of mechanical stimuli. This study might provide useful guidelines for the prevention, diagnosis and treatment strategies of cancer as well as tissue engineering in biomedical applications.

细胞群体行为是基于多细胞间信息和作用协同的复杂力学行为。它不仅在正常生理过程中扮演着重要角色，而且在许多病理过程中起着关键作用 - 如组织形态发育、伤口愈合和癌症的发展和转移等。近年来大量的实验研究证明力学信号（如力学载荷、细胞外基质的力学性质和细胞间相互作用）可以调控甚至支配细胞的群体极化、排列和迁移行为。目前，人们还不能定量理解力学信号调控细胞群体行为的力学机理，在该领域中还有很多基础问题有待解决。为了研究这些问题，本项目基于实验研究和多尺度建模的方法去探索细胞群体行为中的关键力学问题，研究力学环境调控细胞群体行为的定量规律。将发现描述细胞群体行为的关键力学参量，建立力学刺激对细胞群体行为影响的定量关系，从而阐明力学信号对细胞群体极化、排列和迁移行为进行调控的力学机理。本项目的研究将为癌症的诊断、预防和治疗以及组织工程研究提供理论依据。

本项目基于实验和多尺度建模方法研究了探索了细胞群体行为中的关键力学问题，在力学信号对细胞群体极化、排列和迁移行为进行调控的力学机理方面取得了在国内外有影响的研究进展和成果：1）建立了描述群体细胞极化和排列行为的力学模型；2）提出了应力驱动的群体细胞极化和排列行为的力学机制；3）定量研究了影响细胞协同力学行为的力学因素。.研究成果发表在生物力学、物理和材料的重要杂志Nat Comm、Nano Lett、Adv Mater、JMPS和Biophysical Journal等顶级期刊上。共发表论文20篇，其中SCI论文18篇。共参加学术会议26次。组织或参与组织了多个国际、国内会议，包括 “生物力学与生医工程进展西湖论坛”、“第八届全国生物力学青年学者学术研讨会”、 “18th US National congress on Theoretical and Applied Mechanics”、“2018全国固体力学学术会议专题研讨会”。.培养博士11名，硕士4名。已毕业博士2名。2名博士即将毕业。其中1名博士获得北京理工大学优秀博士学位论文。