סמינר בכימיה אורגנית: Designed Biomolecular Condensates: Mechanistic Insights and Applications in Bionanotechnology

Abstract:

Inspired by the role of intracellular liquid-liquid phase separation (LLPS) in formation of membraneless organelles, there is great interest in developing dynamic compartments formed by LLPS of intrinsically disordered proteins (IDPs), short peptides, or by multiple components i.e. peptides and nucleic acids. However, the molecular mechanisms underlying the formation of biomolecular condensates have not been fully elucidated, rendering on-demand design of synthetic condensates with tailored physicochemical functionalities a significant challenge. To address this need, we designed a library of LLPS-promoting peptide building blocks composed of various assembly domains. We show that the LLPS propensity, dynamics, and encapsulation efficiency of compartments can be tuned by changes to the peptide composition. Additionally, we show how the composition of the peptides affect complexation with nucleic acid polymers and in turn, the properties of the condensates. The resulting sequence-structure-function correlation provide the basis for the future development of compartments for a variety of applications. Currently, we explore the nanobiotechnological potential of the designed condensates to serve as microreactors and enzymatic sensors.