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Related Experiment Video

Updated: Jul 16, 2025

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Synthetic symmetry breaking and programmable multicellular structure formation.

Noreen Wauford1, Akshay Patel1, Jesse Tordoff2

  • 1Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Cell Systems
|September 9, 2023
PubMed
Summary
This summary is machine-generated.

Scientists engineered a controllable genetic switch to program cell differentiation and self-organization. This tool precisely controls cell fate probabilities and adhesion, enabling the creation of complex 3D tissue structures from single cell populations.

Keywords:
adhesionagent-based modelbiophysicsmorphogenesissimulationssymmetry breakingsynthetic biology

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Area of Science:

  • Developmental Biology
  • Synthetic Biology
  • Biotechnology

Background:

  • Cellular development involves symmetry breaking into distinct subpopulations that self-organize into complex structures.
  • Existing tools lack control and coupling for recapitulating these developmental processes.
  • Controllable symmetry breaking is crucial for engineering complex tissues and organoids.

Purpose of the Study:

  • To engineer a novel genetic switch for programmable symmetry breaking in cells.
  • To control cell fate commitment probabilities and downstream morphological self-organization.
  • To investigate the relationship between cell-cell adhesion and emergent 3D morphologies.

Main Methods:

  • Engineered a stochastic recombinase genetic switch tunable by small molecules.
  • Utilized small molecule inducers to control commitment probabilities and subpopulation ratios.
  • Manipulated cell-cell adhesion properties of differentiated cell fates.
  • Developed a computational model to analyze experimental results and morphology formation.

Main Results:

  • Achieved programmable symmetry breaking, controlling cell fate commitment and subpopulation ratios.
  • Generated diverse 3D morphologies from a monoclonal cell population by tuning cell adhesion.
  • Computational modeling showed high concordance with experimental data, revealing insights into adhesion-morphology relationships.

Conclusions:

  • The engineered genetic switch enables precise control over cell fate and self-organization.
  • This programmable system facilitates the generation of complex 3D structures for tissue engineering.
  • The tool provides a foundation for advanced organoid engineering and developmental biology studies.