Optimal control of protein copy number

TL;DR

This paper develops a framework for designing optimal control protocols to manipulate protein copy number distributions in cells by dynamically changing chemical potentials, with potential applications in cell signaling and optogenetics.

Contribution

It introduces a method to determine minimum-dissipation control schedules for protein copy numbers in reaction networks, linking thermodynamics with cellular signaling.

Findings

Analytic solutions for linear reaction networks.

Protocols feasible with optogenetic techniques.

Predictions for cell-cell communication dynamics.

Abstract

Cell-cell communication is often achieved by secreted signaling molecules that bind membrane-bound receptors. A common class of such receptors are G-protein coupled receptors, where extracellular binding induces changes on the membrane affinity near the receptor for certain cytosolic proteins, effectively altering their chemical potential. We analyze the minimum-dissipation schedules for dynamically changing chemical potential to induce steady-state changes in protein copy-number distributions, and illustrate with analytic solutions for linear chemical reaction networks. Protocols that change chemical potential on biologically relevant timescales are experimentally accessible using optogenetic manipulations, and our framework provides non-trivial predictions about functional dynamical cell-cell interactions.