Dynamics and Control of Biomolecular Systems

Abstract

Biological cells are complex dynamic systems in which sensing, control, and actuation are orchestrated by networks of active molecules with coupled functions. Cells not only detect and process information, but also leverage that information to direct the assembly of physical structures, such as scaffolds, membranes, and organelles. A productive approach to understanding the design principles governing these multicomponent systems involves the constructive, bottom-up synthesis of biomolecules capable of performing dynamic tasks. Many challenges emerge when building such systems, such as parametric uncertainty, unintended interactions, and the breakdown of signaling modularity, which can be better understood by synthesis efforts outside the cell. I will discuss these challenges in the context of in vitro synthetic biology, which offers a simplified environment for constructing coupled biochemical reaction networks and self-assembling systems. I will begin by describing methods to design artificial nucleic acids (DNA and RNA) that drive the creation of signal generators and components that self-assemble into a variety of structural elements, like filamentous crystals and amorphous condensates. Next, I will explore how these signaling networks and self-assembled structures can be interconnected via the design of nucleic acid sequences, using computational tools to program their interactions. I will then discuss how pulse generators and oscillator circuits can regulate the formation and dissolution of self-assembled physical structures. I will also describe how these techniques have enabled the creation of dynamic, artificial organelles within living cells. These advances contribute to our broader goal of controlling physical matter through biomolecular reactions, paving the way for the development of intelligent biological materials that can sense and make decisions through embedded control programs.