BPS2026 – Collective cell motility of fibroblasts driven by contractile multicellular network formation during compaction of collagen matrix

The complex interplay between cells and the extracellular matrix governs a wide array of physiological processes, from collective cell migration and multicellular patterning to tissue organization, as well as pathological conditions such as wound closure, tissue regeneration, and cancer progression. The mechanical properties of the ECM determine cell behavior and cell fate, while cells, in turn, modify their surrounding ECM to mechanically communicate with each other. To investigate how the actomyosin generated contractile forces of a multicellular network of fibroblasts alter ECM architecture and drive the collective migration of cells during collagen gel compaction, we developed an agent-based network model to explicitly simulate the interaction between cells and the ECM, along with their dynamics. Our results accurately match experimental observations of phase transition in compaction induced by multicellular network formation. Additionally, our model simulates the dynamics of ECM restructuring into organized fiber bundles, leading to the emergence of nematic order driven by the cells. This work sheds light on the importance of the cell’s internal actomyosin in regulating the mechanical properties of the ECM. Understanding how cellular forces drive morphological changes in tissue is at the core of mechanobiology. Investigating the role of mechanics in these model systems can inform the engineering of biomaterials for regenerative tissue applications.