Physical role of the nucleus in cell migration

了解转移性癌细胞是如何移动的，将有助于寻找针对次级肿瘤形成细胞的治疗方法。最近的实验表明，癌细胞的细胞核被破坏，通常比健康细胞软得多，在细胞迁移中发挥着重要作用。具体地说，细胞核被认为参与设定或维持细胞运动的方向。细胞核和细胞骨架(细胞的主要结构体)之间的连接似乎对软3D组织样环境中的迁移至关重要。最后，细胞核是否被卡住，决定了细胞能否成功地通过收缩。该项目将开发理论模型，其预测一旦得到检验，将确定细胞核在细胞迁移中的物理作用。从物理学的角度来看，细胞细胞骨架可以被描述为一种软凝胶状物质，它是“活跃的”或“不平衡的”，这意味着它正在消耗生化能量。最近发展起来的“活性凝胶”理论已经成功地描述了这种类型的材料，该理论已经被证明在模拟细胞运动方面很有用。通常在这样的模型中，细胞的核被忽略，细胞被视为单一材料，然而，这个项目专门讨论了核的作用。在活跃(不平衡)物质物理学的新兴领域中，理解嵌入在活性流体中的被动弹性物体的机械作用是一个具有挑战性的问题。阐明细胞核在细胞迁移中的物理作用将对理解生命物理学的重大挑战做出重要贡献。

Understanding how metastatic cancer cells move will enable the search for therapies targeting secondary tumour forming cells. Recent experiments suggest that the cell nucleus, which is disrupted and generally much softer in cancerous cells compared to healthy cells, plays an important role in cell migration. Specifically the nucleus is thought to be involved in setting or maintaining the direction of cell motion. Connections between the nucleus and the cytoskeleton (the main structural body of the cell) appear to be essential for migration in soft 3D tissue-like environments. Finally whether or not the nucleus gets stuck determines whether a cell successfully squeezes through constrictions. This project will develop theoretical models whose predictions, once tested, will determine the physical roles of the nucleus in cell migration. From a physics perspective the cell cytoskeleton can be described as a soft gel-like material that is "active" or "out of equilibrium" meaning it is consuming biochemical energy. This type of material has been successfully described by the recently developed theory of "active gels", which has already proved useful in modelling cell movement. Usually in such models the nucleus of the cell is ignored and the cell is treated as a single material, however this project specifically addresses the role of the nucleus. Understanding the mechanical roles of a passive elastic object embedded in an active fluid is a challenging problem within the emerging field of the physics of active (out of equilibrium) matter. Elucidating the physical roles of the nucleus in cell migration will make an important contribution to the grand challenge of understanding the physics of life.