Designing biomolecules for adaptive properties

Scientists at the City University of New York have demonstrated a new synthetic methodology to investigate how complex mixtures of biomolecules interact, and spontaneously form dynamic patterns to collectively adapt to changes in their environment. In a breakthrough that helps our understanding of how complex mixtures of biomolecular building blocks can form self-organized patterns, this bottom-up approach could also facilitate the design of novel materials and technologies with similar abilities and attributes.

As reported in the journal Chem [Jain et al. Chem (2022) DOI: 10.1016/j.chempr.2022.03.016], the study, led by Ankit Jain in Rein Ulijn’s lab at CUNY Graduate Center, describes an innovative way of using designed mixtures to develop the type of adaptive properties usually only seen in living systems, providing new knowledge about adaptive biological functions. Such mixtures could one day bring precision sensing of mixtures of molecules, potentially helping in disease detection or identifying compositions of complex mixtures.

The team used a series of test tube experiments to produce biomolecule mixtures with components that are designed to react and interact, before tracking and observing the emergence of the complex patterns the biomolecules spontaneously formed as a response. Proteins are made of the same conserved 20 amino acid building blocks, with each protein usually containing over 100 in a specific sequence. Here, mixtures of specific dipeptides were created, with further complexity coming from the gradual introduction of further dipeptides. An enzyme was also inserted as a catalyst to connect or disconnect dipeptides, enabling them to dynamically recombine and form new peptides with more complex interaction patterns.

The most complex system examined here began with 15 different dipeptides, which reversibly and dynamically combine to form 225 unique tetrapeptides in different patterns, making it possible to track the formation and breakdown of all individual peptides of different sequences. The patterns of interaction in this molecular adaptation were strongly dictated by environmental conditions, including changes in temperature or addition of metabolites, such as ATP.

Rationalizing the rules of organization of mixtures of molecules could enhance our understanding of biology at the molecular level, potentially offering important insight into the chemical origins of biological function. As Jain said: “This understanding could also give rise to completely new ways of creating materials and technologies that incorporate life processes such as adapting, growing, healing and developing new properties when required”.

The team hope to learn how to create mixtures that self-organize and reconfigure depending on their context, thereby displaying a functionality, specific structure, optical or electronic property. They are also investigating systems that can report and adjust metabolite levels relevant to diseased states. “Systematically designing mixtures and tracking their behavior allows us to make fundamental observations about how mixtures of molecules become functional collectives”, said Ulijn. “We were able to detail how these chemical systems absorb changes in external conditions to form specific patterns of build-up and breakdown”.

“We were able to detail how these chemical systems absorb changes in external conditions to form specific patterns of build-up and breakdown”Rein Ulijn