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Programmed assembly of 3-dimensional microtissues with defined cellular connectivity.

Zev J Gartner1, Carolyn R Bertozzi

  • 1Department of Chemistry, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720.

Proceedings of the National Academy of Sciences of the United States of America
|March 11, 2009
PubMed
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Scientists created novel multicellular microtissues with programmed cell connections using DNA-functionalized cells. This breakthrough allows precise control over tissue assembly and the construction of complex cellular networks for research.

Area of Science:

  • Biotechnology
  • Tissue Engineering
  • Synthetic Biology

Background:

  • Multicellular organs rely on precise cell arrangement and communication for function.
  • Replicating complex in vivo tissue organization in vitro is challenging.
  • Understanding cell-cell interactions is crucial for developing functional tissue models.

Purpose of the Study:

  • To develop a bottom-up method for synthesizing microtissues with programmed cell connectivity.
  • To control the assembly of multicellular structures with defined cell-cell contacts.
  • To engineer functional paracrine signaling networks within engineered microtissues.

Main Methods:

  • Functionalizing cells with short oligonucleotides to create specific adhesive properties.
  • Utilizing DNA sequence hybridization for controlled self-assembly of multiple cell types.

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Last Updated: Jun 25, 2026

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  • Analyzing the kinetics of cell assembly based on DNA sequence complexity, density, and cell concentration.

    • Main Results:

    • Demonstrated successful bottom-up synthesis of microtissues with programmed cell connectivity.
    • Established that assembly kinetics are tunable by controlling DNA sequence and cell concentration.
    • Engineered microtissues with defined cell composition and stoichiometry.
    • Successfully constructed a paracrine signaling network within isolated 3D microtissues.

    Conclusions:

    • Developed a novel strategy for engineering multicellular microtissues with precise control over cell-cell interactions.
    • This method enables the creation of complex, functional tissue models in vitro.
    • The technology holds potential for advancing tissue engineering and regenerative medicine applications.