Programmed assembly of 3-dimensional microtissues with defined cellular connectivity
- Zev J. Gartnera,1 and
- Carolyn R. Bertozzia,b,c,d,2
- Departments of aChemistry and
- bMolecular and Cell Biology,
- cHoward Hughes Medical Institute, University of California, Berkeley, CA 94720; and
- dThe Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720
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Contributed by Carolyn R. Bertozzi, January 23, 2009 (sent for review November 26, 2008)
Abstract
Multicellular organs comprise differentiated cell types with discrete yet interdependent functions. The cells' spatial arrangements and interconnectivities, both critical elements of higher-order function, derive from complex developmental programs in vivo and are often difficult or impossible to emulate in vitro. Here, we report the bottom-up synthesis of microtissues composed of multiple cell types with programmed connectivity. We functionalized cells with short oligonucleotides to impart specific adhesive properties. Hybridization of complementary DNA sequences enabled the assembly of multicellular structures with defined cell–cell contacts. We demonstrated that the kinetic parameters of the assembly process depend on DNA sequence complexity, density, and total cell concentration. Thus, cell assembly can be highly controlled, enabling the design of microtissues with defined cell composition and stoichiometry. We used this strategy to construct a paracrine signaling network in isolated 3-dimensional microtissues.
Footnotes
- 2To whom correspondence should be addressed. E-mail: crb{at}berkeley.edu
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Author contributions: Z.J.G. and C.R.B. designed research; Z.J.G. performed research; Z.J.G. and C.R.B. analyzed data; and Z.J.G. and C.R.B. wrote the paper.
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↵1Present address: Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158.
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The authors declare no conflict of interest.
