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

Umnia Doha, Onur Aydin, Md Saddam Hossain Joy, Bashar Emon, William Drennan, M. Taher A. Saif

Research output: Contribution to journalArticlepeer-review


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. Statement of significance: Macroscopic compaction of in vitro collagen gels is mediated by collective mechanical interaction of cells. Previous studies on cell-induced ECM compaction suggest the existence of a critical cell density and phase transition associated with this phenomenon. Cell-mediated mechanical remodeling and global compaction of ECM has mostly been studied at steady state. Our study reveals a link between a transition in cell dynamics and material microstructure as cells collectively compact collagen gels. It underscores the significance of temporal evolution of these cell-ECM systems in understanding the mechanism of such collective action and provides insights on the process from a mechanistic viewpoint. These insights can be valuable in understanding dynamic pathological processes such as, cancer progression and wound healing, as well as engineering biomaterials and regenerative tissue mimics.

Original languageEnglish (US)
Pages (from-to)290-301
Number of pages12
JournalActa Biomaterialia
StatePublished - Dec 2022
Externally publishedYes


  • Collective cell behavior
  • Critical cell-cell distance
  • Phase transition
  • Transient ECM remodeling

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Biotechnology
  • Biomedical Engineering
  • Biomaterials


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