NSF-BSF:Communication across Supramolecular Biomaterial Networks

Technical Summary: Liquid droplet coacervate formation through phase separation is driven by the positive entropy of backbone desolvation allowing for intermolecular enthalpic side-chain complementarity to dominate secondary nucleation events. Importantly, this hardwiring into environmental conditions serves as a molecular “Lamarckian-like” analog computer, providing specific functional assemblies templated from the initial coacervate. To define how environmental conditions and molecular templates organize each nucleation step, and to characterize the range of potential emerging functions in these hierarchical formations, we combine the expertise and perspectives provided by our labs’ systems chemistry approaches to build cooperative communication networks between different material phases. Our objectives will be achieved through 3 aims focused on creating biomaterial forms guided by the evolved achievements of bacterial cell information exchange: pili attachments (or more generally fimbriae) for nucleic acid exchange, small molecule reaction-diffusion networks, and extended nanowire energy transfer between condensates. These studies will provide the first strategies for creating self-assembling informational coacervates of cooperative and functionally synergistic synthetic materials that complement and expand the properties of living systems. Non-technical Summary Intrinsically Disordered (ID) synthetic materials have revolutionized the construction of transparent and moldable materials that are now used for so many societal applications. In contrast, Nature’s polypeptides have evolved novel functions ranging from scaffolding to locomotion, from material transport and energy acquisition to catalysis, signaling, and organismal defense, all based on a precisely folded three-dimensional protein structure. While backbone dynamics, side chain electrostatics, hydrophobics, van der Waals packing, and desolvation all contribute to protein folding energetics, these forces depend on media dielectrics, pH, temperature, external surfaces, and phase transitions, making environmental adaptability critical.1,2 Indeed proteins evolved intrinsically disordered regions (IDRs) that function as adaptable interfaces for mutualistic co-assemble, and on an even larger scale, liquid-liquid phase separated coacervates, known as biomolecular condensates (BMC) or membraneless organelles.3,4 BMCs appear responsible for processing environmental information, and most recently, a heptad repeat sequence within the glutamine-rich region (QRR) of the ID Whi3 protein was shown to be necessary and sufficient as a rheostat temperature control knob that controls both nuclear division and polarized growth in the fungus Ashbya gossypii. Within its compact genome of roughly 4,600 genes, this dynamic BMC provides Lamarckian-like evolutionary adaptation connecting to the digital genome, raising critical questions as to how general conformational dynamics might be processed as specific analog outputs. As we continue to learn the rules for controlling BMCs to function in order transitions, we have the potential to construct BMC peptide assemblies that access alternate critical functional assemblies for new life processes, including polymer translation and electron transfer chains for energy acquisition, and are poised to define other cooperative functions able to expand the functional adaptability of living systems. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.