The Problem
Cells must interpret complex molecular environments and make decisions, but scientists still do not fully understand how these processes emerge from the physical organization of molecules.
Research
Cells May Use Condensates to Make Molecular Decisions
New models reveal how molecular organization could help cells classify information and respond to signals
Our Idea
Researchers developed theoretical models showing that biomolecular condensates can classify chemical signals and guide cellular decision-making directly through the same physics that organizes molecules inside cells around surfaces, like dew drops on a leaf.
Why It Matters
The findings reveal a new role for condensates in biology and could inform the design of synthetic cells, molecular sensors, and programmable biomaterials.
Our Team
Professor Krishna Shrinivas, PhD candidate Ethan Halingstad, et al.
A team led by Northwestern Engineering’s Krishna Shrinivas has developed theoretical models showing that the same physics that creates biomolecular condensates, dynamic compartments that concentrate proteins and nucleic acids, could also help cells make decisions that ultimately shape cell behavior and function. Through theoretical models, the team demonstrated how mixtures of molecules recognize surfaces with subtly different chemical compositions and assemble different condensates on each surface. This molecular classification could allow cells to distinguish among molecular cues and generate different biological responses.
For example, the researchers found that condensates with different functions, such as gene activation or repression, could selectively form at distinct locations along DNA, suggesting a new way cells might process information and control complex biological functions.
“Every cell must interpret a crowded and noisy molecular environment—for example, deciding which genes to activate or how to respond to a signal,” Shrinivas said. “Our findings suggest that cells may use the same physical process that organizes their contents to help make these decisions. In the longer term, these principles could inform the design of synthetic cells, molecular sensors, and programmable biomaterials that recognize complex chemical environments and respond appropriately.”
The researchers also found that condensates can create complex decision boundaries and that the same mixture of molecules can be reprogrammed to solve new classification tasks without changing the underlying molecular interactions, giving the system adaptability.
The findings reveal a broader role for condensates beyond simply organizing molecules inside cells. The researchers showed that the physical process of condensate formation can enable cells to interpret molecular signals and generate adaptable responses. The work offers new insight into how cells organize information and carry out the processes that underlie health and disease.
Shrinivas is an assistant professor of chemical and biological engineering at the McCormick School of Engineering. A member of the Center for Synthetic Biology and the National Institute of Theory and Mathematics in Biology, Shrinivas presented this work in the paper “Combinatorial Decision-Making Driven by Multicomponent Surface Condensates.” The work was published in July and was featured on the cover of the Proceedings of the National Academy of Sciences. Collaborators included Ethan Halingstad from Northwestern, first author Aidan Zentner and Michael Brenner (Harvard University), Cameron Chalk and Erik Winfree (California Institute of Technology), and Arvind Murugan (University of Chicago). Halingstad is a PhD candidate in chemical and biological engineering.
Winfree said the work could provide a foundation for designing new types of synthetic biological systems that use physical principles such as condensation to carry out specific tasks.
“As we build molecular systems, we need to understand which biological mechanisms are best suited for different tasks,” Winfree said. “Certainly, it would be exciting if these principles help us understand biological decision-making, such as gene regulation. I am personally fascinated by the prospect of ‘programming’ synthetic cells and understanding what sorts of physical and chemical mechanisms, such as condensation, are the right tools for a given task.”
“Our work helps define what surface condensation can and cannot accomplish as a form of molecular computation,” Shrinivas said. “By studying its capabilities and limitations, we can better understand how these systems solve classification problems and where their boundaries lie.”
Moving forward, the team plans to explore how condensates could be harnessed in synthetic systems to perform new types of molecular classification. By building experimental models, including promising DNA-based systems, researchers hope to demonstrate how these “smart droplets” could recognize and respond to complex chemical environments. They also aim to uncover the broader information-processing capabilities of condensates, including whether their dynamic behavior could allow them to adapt, learn patterns, or make more sophisticated decisions.