Biomolecular Condensates Can Induce Local Membrane Potentials.

Biomolecular condensates are a ubiquitous component of cells, known for their ability to selectively partition and compartmentalize biomolecules without the need for a lipid membrane. Nevertheless, condensates have been shown to interact with lipid membranes in diverse biological processes, such as autophagy and T-cell activation. Since many condensates are known to have a net surface charge density and associated electric potential(s), here it is hypothesized that wetting of a membrane by a condensate can locally alter membrane potential. Using an electrochromic dye and a model system that encodes electrostatic features present in many cellular systems, it is demonstrated that poly-lysine (polyK)/adenosine triphosphate (ATP) complex coacervates induce a localized membrane potential in Giant Unilamellar Vesicles (GUVs). This effect diminishes with increasing salt concentration and higher ATP-to-polyK ratios, underscoring the key role of condensate charge and corresponding Galvani potential. Numerical modeling of the condensate-membrane interface using an electro-thermodynamic framework supports the experimental findings and highlights parameters expected to play key roles in the effect. These results have broad implications for biological processes regulated by membrane potential, particularly in contexts such as neuronal signaling, where condensate interactions with membranes may play a previously unrecognized regulatory role.