发表机构
Mathematical Institute, Leiden University; Institute of Biology, Leiden University（莱顿大学数学研究所; 莱顿大学生物学研究所）
机构由 AI 辅助整理，请以论文原文为准。AI 中文总结
该研究开发了耦合CPM与离散可变形ECM的3D混合框架，可模拟细胞诱导的ECM重塑，揭示ECM刚度、纤维交联对细胞收缩与基质重塑的影响，为多细胞行为研究提供通用3D平台。
AI 中文摘要
细胞外基质（ECM）是一种纤维状动态网络，在发育、稳态及疾病中发挥关键作用。细胞既对ECM产生响应，又会重塑ECM，二者存在塑造组织的机械相互作用。为研究这些相互作用，已开发出计算模型，分别模拟ECM力学或细胞行为。细胞Potts模型（CPM）是一种灵活的基于细胞的框架，已扩展至诸多生物过程，包括与离散可变形纤维网络耦合。然而，迄今为止，这种耦合仅应用于二维场景，而三维设定在生物学上更具相关性。本文提出一种3D混合框架，将CPM与ECM的离散可变形表示耦合，该模型可显式模拟细胞诱导的ECM重塑，包括纤维重定向与基质致密化。通过整合通过静态黏附点产生的收缩力，模型可捕捉ECM弹性与纤维刚度如何影响细胞形状。模拟结果显示，由纤维交联控制的ECM刚度会抵抗收缩并达到平衡，而交联密度可调节纤维排列与局部基质积累。该框架为研究细胞-ECM力学提供了通用平台，支持未来在真实3D环境中对多细胞行为的研究。
英文摘要
The extracellular matrix (ECM) is a fibrous and dynamic network that plays a critical role in development, homeostasis, and disease. Cells both respond to and remodel the ECM, engaging in a mechanical reciprocity that shapes tissues. To study these interactions, computational models have been developed that simulate either ECM mechanics or cell behavior. The Cellular Potts Model (CPM) is a flexible cell-based framework that has been extended to many biological processes, including coupling to a discrete deformable fiber network. So far, however, this extension has only been applied in two dimensions, even though a three-dimensional setting is biologically more relevant. Here, we present a 3D hybrid framework that couples the CPM with a discrete and deformable representation of the ECM. This model enables explicit simulation of cell-induced ECM remodeling, including fiber reorientation and matrix densification. By incorporating contractile forces through static adhesion points, the model captures how ECM elasticity and fiber stiffness influences cell shape. The simulations show that ECM stiffness, controlled by fiber crosslinking, resists contraction and reaches equilibrium, while crosslink density modulates fiber alignment and local matrix accumulation. This framework provides a versatile platform for studying cell-ECM mechanics and supports future studies of multicellular behavior in realistic 3D environments.
CommentsIn revision for Biomechanics and Modeling in Mechanobiology
