Biomolecular Condensates can Induce Local Membrane Potentials

Abstract

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), we hypothesized that they can induce a local membrane potential. Using an electrochromic dye, we demonstrate that poly-lysine/ATP condensates induce a localized membrane potential in Giant Unilamellar Vesicles. This effect diminishes with increasing salt concentration and higher ATP-to-poly-lysine ratios, underscoring the key role of condensate charge. Numerical modeling of the condensate-membrane interface using an electro-thermodynamic framework supports our experimental findings and highlights parameters expected to play a key role 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.