Emergence of collective behavior and phase transition in multicellular systems through long-range mechanical interaction

Doha, Umnia

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https://hdl.handle.net/2142/120415 Copy

Description

Title

Emergence of collective behavior and phase transition in multicellular systems through long-range mechanical interaction

Author(s)

Doha, Umnia

Issue Date

2023-04-27

Director of Research (if dissertation) or Advisor (if thesis)

Saif, Md Taher Abu

Doctoral Committee Chair(s)

Saif, Md Taher Abu

Committee Member(s)

• Wagoner Johnson, Amy
• Brieher, William M
• Kersh, Mariana E

Department of Study

Mechanical Sci & Engineering

Discipline

Mechanical Engineering

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Collective behavior
• phase transition
• mechanical interaction
• multicellular systems

Abstract

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 initiates such complex collective processes is still not clear. Biomimetic tissue constructs comprising of 3D extracellular matrix (ECM) protein and cells are known to compact in response to contractile cell force and serve as an excellent in vitro model to investigate the onset of collective behavior in the multicellular system. Both experimental and theoretical studies have been conducted to unravel the mechanism of compaction of tissue by cells. However, a comprehensive understanding of the process that correlates cell-level microscopic mechanical interaction between cell and extracellular matrix to the general biophysical rules for the emergence of collective behavior cell-ECM system still does not exist. Here, we report that cells in a 3D Extra Cellular Matrix (ECM) initiate collective behavior by forming a cell-ECM network when the cells are within a critical distance from each other. Beyond the critical distance, the network does not emerge. We studied the compaction of free-floating disc-shaped collagen gels seeded with fibroblast cells. A sharp transition in the degree of compaction was observed as a function of cell-cell distance, reminiscent of first-order phase transition in multi-component physical systems. Within the critical distance, cells remodel the ECM irreversibly and form densified collagen fiber bridges between each other resulting in the network. Following the formation of the cell network, global compaction takes place by long-range mechanical communication of cells through these bridges in a positive feed-forward way. We have introduced a technique to decouple the extracellular mechanical stimuli from the intracellular biochemical signaling to understand the role of cell-ECM mechanical crosstalk in driving compaction. This was done by inserting cell-sized inert polystyrene (PS) beads in cell-populated gels, which revealed that cell-cell interaction is primarily mechanical - cells can “see” their neighbors through mechano-sensing. Beyond the critical distance, cells do not interact. They do not remodel the matrix, they only deform the matrix reversibly in a transient fashion with no memory of history, thus maintaining the disorder. Network formation seems to be a necessary and sufficient condition to trigger collective behavior and disorder-to-order transition. We have experimentally demonstrated the significance of the nonlinear mechanical properties of ECM on the onset of cell network formation by quantifying strain on ECM at the cellular protrusion level. From confocal reflectance time-lapse imaging of live cells in collagen, we have shown the temporal evolution of buckling of the collagen fibers in response to long-range force transmission between cells. Based on our observations, we have proposed a two-stage mechanistic model that correlates the microscopic mechanical interaction between cells to the macroscopic compaction of tissue.

Graduation Semester

2023-05

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/120415

Copyright and License Information

Copyright 2023 Umnia Doha

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