Department of Mechanical and Aerospace Engineering, University at Buffalo, The State University of New York, Buffalo, NY, USA.
Department of Physics, University at Buffalo, The State University of New York, Buffalo, NY, USA.
Nat Commun. 2024 Sep 3;15(1):7686. doi: 10.1038/s41467-024-51840-6.
The internal microenvironment of a living cell is heterogeneous and comprises a multitude of organelles with distinct biochemistry. Amongst them are biomolecular condensates, which are membrane-less, phase-separated compartments enriched in system-specific proteins and nucleic acids. The heterogeneity of the cell engenders the presence of multiple spatiotemporal gradients in chemistry, charge, concentration, temperature, and pressure. Such thermodynamic gradients can lead to non-equilibrium driving forces for the formation and transport of biomolecular condensates. Here, we report how ion gradients impact the transport processes of biomolecular condensates on the mesoscale and biomolecules on the microscale. Utilizing a microfluidic platform, we demonstrate that the presence of ion concentration gradients can accelerate the transport of biomolecules, including nucleic acids and proteins, via diffusiophoresis. This hydrodynamic transport process allows localized enrichment of biomolecules, thereby promoting the location-specific formation of biomolecular condensates via phase separation. The ion gradients further impart directional motility of condensates, allowing them to exhibit enhanced diffusion along the gradient. Coupled with a reentrant phase behavior, the gradient-induced enhanced motility leads to a dynamical redistribution of condensates that ultimately extends their lifetime. Together, our results demonstrate diffusiophoresis as a non-equilibrium thermodynamic force that governs the formation and transport of biomolecular condensates.
活细胞的内部微环境是不均匀的,包含许多具有不同生物化学特性的细胞器。其中包括无膜的、相分离的生物分子凝聚物,它们富含特定于系统的蛋白质和核酸。细胞的不均匀性导致化学、电荷、浓度、温度和压力存在多个时空梯度。这种热力学梯度可能导致生物分子凝聚物的形成和运输的非平衡驱动力。在这里,我们报告离子梯度如何影响生物分子凝聚物在介观尺度和生物分子在微观尺度上的输运过程。利用微流控平台,我们证明离子浓度梯度的存在可以通过扩散泳来加速生物分子(包括核酸和蛋白质)的运输。这种流体动力学输运过程允许生物分子局部富集,从而通过相分离促进生物分子凝聚物的位置特异性形成。离子梯度进一步赋予凝聚物的定向运动性,使其能够沿着梯度增强扩散。与再入相行为相结合,梯度诱导的增强运动导致凝聚物的动态再分配,最终延长其寿命。总之,我们的结果表明扩散泳是一种非平衡热力学力,它控制着生物分子凝聚物的形成和输运。