Please join Yale Chemistry for the Fall 2025 Student-Invited Biophysical Chemistry Seminar with Prof. Carlos Baiz, Associate Professor, from University of Texas Austin.
Abstract: Biomolecular condensates (BMCs), also referred to as membraneless organelles are stabilized by a complex interplay of electrostatic interactions, cation-π, π-π stacking, and hydrogen bonding, provide dynamic environments essential for regulating cellular function. Water is confined within nanometer-scale channels, profoundly influencing the interactions and dynamics of biomolecular constituents. Understanding the structural and dynamical properties of BMCs is important to explain their phase stability and ultimately describe their roles in cellular processes.
We use ultrafast two-dimensional infrared (2D IR) spectroscopy and MD simulations, to investigate the picosecond H-bond dynamics and structural properties of biomolecules in model BMCs. The results reveal that the hydrogen-bond dynamics are sequence-dependent, with dynamics in the condensate phase being approximately 2-3 times slower than in bulk water, underscoring the role of confinement and biomolecular interactions in modulating the local environment.
Simulations uncover interactions between arginine side-chains the phosphate backbone of nucleic acids as a main stabilizing force. Experiments further demonstrate significant changes in secondary structure upon phase separation, with residual structures varying based on the type of condensate. These differences in residual secondary structure point to the diverse roles of condensates in cellular functions and their potential implications for aggregation-prone sequences. This work sheds light on the interplay between molecular interactions, structural stability, and the confined environment within biomolecular condensates, offering new perspectives on their biophysical properties and potential pathological implications.
