Physical Principles Shaping Biomolecular Condensates

Coordinators: Jerelle Joseph, Frank Jülicher, Stephanie Weber, and David Zwicker

Scientific Advisors: Amy Gladfelter

Living cells contain a myriad of biomolecular condensates that organize molecules in space and time. These membrane-less compartments participate in virtually all cellular functions and their dysregulation contributes to disease. Principles from polymer physics and thermodynamics have been used to provide mechanistic insight into the formation and dissolution of biomolecular condensates. However, a strong disconnect between the simplest theories of phase separation and the actual complexity observed in cells remains. Indeed, whether and how classical physical theories can be applied to the nonequilibrium, multicomponent, and fluctuating environment within cells is still unclear. To address this pressing gap, new physical theories, techniques, and approaches are necessary to understand and predict the behavior of biomolecular condensates in living cells.

This program will bring together experts in soft condensed matter physics, molecular simulations, and biophysics to explore fundamental properties of condensates – such as lifetime, nonequilibrium activity, size, mechanochemical properties, and architecture – and the interplay between them. Through sustained interdisciplinary discussions, the program intends to develop new theoretical frameworks and integrative multiscale approaches that accurately describe biomolecular condensates inside cells.