细胞体积对细胞群体迁移的调控机制研究

In current experimental and theoretical studies about collective cell migration, researchers usually focus on some limited aspects, such as the cell-cell interaction, cell-substrate interaction and cortical tension of cells, but neglect the important influence of the cellular volume. Although dramatic cellular volume changes have been observed in experiments, the experimental or theoretical studies about how the cell volume changes over time and space during collective cell migration and how cell volume changes affect the collective cell migration are still lacking. Therefore, in this project we aim to study how the cell volume changes over time and space, and illuminate the mechanism of the mechanical waves and rigidity transition during collective cell migration. Especially, we will study how the cell volume changes, external forces, the mechanical properties of substrate and physical confinement influence the collective cell migration. Finally, we will develop a theory about the coupling between the cell volume and the stress to explain the experimental data. The results of this study will deepen our understanding about the migration of cancer cells, wound healing and morphogenesis, and thus they will also have scientific significance and potential applications.

目前在细胞力学领域关于细胞群体迁移的实验和理论研究中，研究者通常只关注细胞-细胞相互作用、细胞-基底相互作用、细胞皮层的收缩力等因素，却忽略了细胞体积的重要影响。尽管实验中已经观测到细胞体积的显著变化，但是到目前为止还没有任何理论或者实验系统研究过在细胞群体迁移过程中的细胞体积的空间和时间变化，以及细胞体积调控如何影响细胞群体迁移这些基本问题。针对这些问题，本项目拟研究在细胞群体迁移过程中细胞体积的空间、时间分布，阐明细胞单层内机械波的发生机制，测量细胞单层从群体迁移到阻塞这个液-固转变过程中的细胞体积的实时变化和空间分布，并研究细胞体积调控、外力、基底力学性质、受限程度这些控制因素对细胞群体迁移的影响，建立关于细胞体积与细胞应力状态耦合机制的基本模型。本项目的研究对理解癌细胞迁移、伤口愈合和形貌发生等生理和病理问题有重要的科学意义和潜在的临床应用价值。

本项目围绕细胞体积与细胞应力状态耦合机制这一科学问题开展了较为系统和深入的理论和实验研究，取得了若干重要研究进展和创新成果：（1）研究了细胞间水的交换对细胞体积和细胞单层应力分布的影响；（2）阐明了细胞间水的交换可以诱导波的产生，从而揭示了一个与力学-化学反馈机制无关的波的产生机制；（3）测量了细胞单层从群体迁移到阻塞这个液-固转变过程中的细胞体积的实时变化和空间分布，揭示了细胞体积调控、细胞密度这些控制因素对细胞群体迁移的影响，并进一步建立了关于细胞体积与细胞应力状态耦合机制的理论模型。本项目共在本领域重要国际、国内期刊发表论文15篇，包括《Physical Review Letters》，《J. Mech. Phys. Solids.》，《Biophysical Journal》，《Soft Matter》及《ACS Applied Materials & Interfaces》等杂志。在项目执行期间培养了9名博士和3名硕士，项目负责人获得“国家杰出青年基金项目”资助。