Gurunian Anthony, Lasker Keren, Deniz Ashok A
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037.
bioRxiv. 2024 Dec 27:2024.12.27.630407. doi: 10.1101/2024.12.27.630407.
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.
生物分子凝聚物是细胞中普遍存在的成分，以其在无需脂质膜的情况下选择性分离和分隔生物分子的能力而闻名。然而，已证明凝聚物在多种生物过程中与脂质膜相互作用，如自噬和T细胞活化。由于已知许多凝聚物具有净表面电荷密度和相关电势，我们推测它们可以诱导局部膜电位。使用一种电致变色染料，我们证明聚赖氨酸/ATP凝聚物在巨型单层囊泡中诱导局部膜电位。随着盐浓度的增加和ATP与聚赖氨酸比例的升高，这种效应减弱，突出了凝聚物电荷的关键作用。使用电热力学框架对凝聚物 - 膜界面进行数值建模支持了我们的实验结果，并突出了预计在该效应中起关键作用的参数。这些结果对由膜电位调节的生物过程具有广泛影响，特别是在神经元信号传导等情况下，其中凝聚物与膜的相互作用可能发挥以前未被认识到的调节作用。
