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Nat Nanotechnol. 2013 Aug;8(8):602-8. doi: 10.1038/nnano.2013.132. Epub 2013 Jul 14.

Molecular crowding shapes gene expression in synthetic cellular nanosystems.

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  • 1Lane Center for Computational Biology, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.

Abstract

The integration of synthetic and cell-free biology has made tremendous strides towards creating artificial cellular nanosystems using concepts from solution-based chemistry, where only the concentrations of reacting species modulate gene expression rates. However, it is known that macromolecular crowding, a key feature in natural cells, can dramatically influence biochemical kinetics via volume exclusion effects, which reduce diffusion rates and enhance binding rates of macromolecules. Here, we demonstrate that macromolecular crowding can increase the robustness of gene expression by integrating synthetic cellular components of biological circuits and artificial cellular nanosystems. Furthermore, we reveal how ubiquitous cellular modules, including genetic components, a negative feedback loop and the size of the crowding molecules can fine-tune gene circuit response to molecular crowding. By bridging a key gap between artificial and living cells, our work has implications for efficient and robust control of both synthetic and natural cellular circuits.

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PMID:
23851358
[PubMed - indexed for MEDLINE]
PMCID:
PMC3951305
Free PMC Article

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