Combinatorial decision-making driven by multicomponent surface condensates

A Aidan Zentner (School of Engineering and Applied Sciences, Harvard University) E Ethan V. Halingstad (Department of Chemical and Biological Engineering, Northwestern University) C Cameron Chalk (Computation and Neural Systems, California Institute of Technology) M Michael P. Brenner A Arvind Murugan (Department of Physics) E Erik Winfree (Computation and Neural Systems, California Institute of Technology) K Krishna Shrinivas (Department of Chemical and Biological Engineering, Northwestern University)

Abstract

Living organisms rely on molecular networks, such as gene circuits and signaling pathways, for information processing and robust decision-making in crowded, noisy environments. Recent advances show that interacting biomolecules self-organize by phase transitions into coexisting spatial compartments called condensates, often on cellular surfaces such as chromatin and membranes. In this paper, we demonstrate that multicomponent fluids can be designed to recruit distinct condensates to surfaces with differing compositions, performing a form of surface classification by condensation. We draw an analogy to multidimensional classification in machine learning and explore how hidden species, analogous to hidden nodes, expand the expressivity and capacity of these interacting ensembles to facilitate complex decision boundaries. By simply changing levels of individual species, we find that the same molecular repertoire can be reprogrammed to solve new tasks. Together, our findings suggest that the physical processes underlying biomolecular condensates can encode and drive adaptive information processing beyond compartmentalization.

Article Details

Volume / Issue Vol. 123, Issue 27
Published July 07, 2026
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (7)

A

Aidan Zentner

School of Engineering and Applied Sciences, Harvard University

E

Ethan V. Halingstad

Department of Chemical and Biological Engineering, Northwestern University

C

Cameron Chalk

Computation and Neural Systems, California Institute of Technology

M

Michael P. Brenner

A

Arvind Murugan

Department of Physics

E

Erik Winfree

Computation and Neural Systems, California Institute of Technology

K

Krishna Shrinivas

Department of Chemical and Biological Engineering, Northwestern University