Lipid membrane topographies are regulators for the spatial distribution of liquid protein condensates

Abstract

Liquid protein condensates play important roles in orchestrating subcellular organization and in serving as hubs for biochemical reactions. Recent studies have established associations between lipid membranes and proteins capable of forming liquid condensates, and shown that liquid protein condensates can remodel lipid membranes. However, little is known about how the topography of membranes affects liquid condensates. Here, we devised a cell-free system to reconstitute liquid condensates on lipid membranes with microstructured topographies and demonstrated an important role of lipid membranes topography as a biophysical regulator. By employing membrane surfaces designed with microwells, we found that liquid condensates assemble into orderly patterns. Furthermore, we demonstrated that membrane topographies influence the shape of liquid condensates. Finally, we showed that capillary forces, mediated by membrane topographies, led to the directed fusion of liquid condensates. Our results demonstrate that membrane topography is a potent biophysical regulator for the localization and shape of mesoscale liquid protein condensates.