Disorder to order transition in cell-ECM systems mediated by cell-cell collective interactions

Cells in functional tissues execute various collective activities to achieve diverse ordered processes including wound healing, organogenesis, and tumor formation. How a group of individually operating cells initiate such complex collective processes is still not clear. Here, we report that cells in 3D extracellular matrix (ECM) initiate collective behavior by forming cell-ECM network when the cells are within a critical distance from each other. We employed compaction of free-floating (FF) 3D collagen gels with embedded fibroblasts as a model system to study collective behavior and found a sharp transition in the amount of compaction as a function of cell-cell distance, reminiscent of phase transition in materials. Within the critical distance, cells remodel the ECM irreversibly, and form dense collagen bridges between each other resulting in the formation of a network. Beyond the critical distance, cells exhibit Brownian dynamics and only deform the matrix reversibly in a transient manner with no memory of history, thus maintaining the disorder. Network formation seems to be a necessary and sufficient condition to trigger collective behavior and a disorder-to order transition.

Recommended citation: U Doha, O Aydin, MSH Joy, B Emon, W Drennan, MTA Saif, Disorder to order transition in cell-ECM systems mediated by cell-cell collective interactions, Acta Biomaterialia, 154, 290-301, 2022, https://doi.org/10.1016/j.actbio.2022.10.012.
Download Paper