Molecular crowding shapes gene expression in synthetic cellular nanosystems

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacteriophage T7 / genetics
  • Bacteriophage T7 / metabolism
  • Computer Simulation
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / isolation & purification*
  • Diffusion
  • Gene Expression*
  • Macromolecular Substances / chemistry
  • Molecular Structure
  • Nanotechnology / methods*
  • Promoter Regions, Genetic
  • Viral Proteins / genetics
  • Viral Proteins / isolation & purification*


  • Macromolecular Substances
  • Viral Proteins
  • bacteriophage T7 RNA polymerase
  • DNA-Directed RNA Polymerases