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Updated: Jan 17, 2026

Automated Robotic Liquid Handling Assembly of Modular DNA Devices
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Efficiency-fluctuation trade-offs in biomolecular assembly processes.

Brayden Kell1, Andreas Hilfinger1

  • 1University of Toronto, University of Toronto, Department of Physics, Toronto, Ontario, Canada M5S 1A7 and Department of Chemical & Physical Sciences, Mississauga, Ontario, Canada L5L 1C6.

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Cellular processes exhibit unavoidable trade-offs between assembly efficiency and molecular fluctuations. Combining feedback control with distinct subunit synthesis rates is necessary to overcome this generalized efficiency-fluctuation trade-off.

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Area of Science:

  • Systems Biology
  • Biophysics
  • Molecular Biology

Background:

  • Stochastic fluctuations in molecular abundances cause cell-to-cell variability.
  • Previous studies suggested an efficiency-fluctuation trade-off in cellular assembly processes.
  • Contradictory findings on noise filtering properties of efficient assembly processes prompted further investigation.

Purpose of the Study:

  • To investigate the applicability of the efficiency-fluctuation trade-off in a broader range of assembly processes.
  • To determine conditions for overcoming the trade-off and mitigating molecular fluctuations.
  • To reconcile conflicting results regarding noise filtering in efficient assembly.

Main Methods:

  • Theoretical analysis of reaction dynamics in cellular networks.
  • Examination of generalized assembly processes with arbitrary interactions.
  • Numerical simulations to illustrate control strategies and their effects.

Main Results:

  • A broader class of assembly processes is subject to an efficiency-fluctuation trade-off diverging at high efficiency.
  • Efficient assembly processes acting as noise filters represent a singular limit.
  • Overcoming the trade-off requires combining feedback control with distinct subunit synthesis rates.

Conclusions:

  • The efficiency-fluctuation trade-off is a general feature of many cellular assembly processes.
  • Biomolecular integral controllers exemplify strategies to overcome this trade-off.
  • The precise control adjustments needed to avoid diverging fluctuations remain an open question.