Institute for Applied Physics, University of Tübingen, 72076 Tübingen, Germany.
Institut Max von Laue - Paul Langevin (ILL), CS20156, F-38042 Grenoble, France.
Langmuir. 2021 Jan 12;37(1):139-150. doi: 10.1021/acs.langmuir.0c02618. Epub 2021 Jan 4.
Proteins are ubiquitous and play a critical role in many areas from living organisms to protein microchips. In humans, serum albumin has a prominent role in the foreign body response since it is the first protein which will interact with, e.g., an implant or stent. In this study, we focused on the influence of salts (i.e., different cations (Y, La) and anions (Cl, I) on bovine serum albumin (BSA) in terms of its bulk behavior as well as the role of charges for protein adsorption at the solid-liquid interface in order to understand and control the underlying molecular mechanisms and interactions. This is part of our group's effort to gain a deeper understanding of protein-protein and protein-surface interactions in the presence of multivalent ions. In the bulk, we established two new phase diagrams and found not only multivalent cation-triggered phase transitions, but also a dependence of the protein behavior on the type of anion. The attractive interactions between proteins were observed to increase from Cl < NO < I, resulting in iodide preventing re-entrant condensation and promoting liquid-liquid phase separation in bulk. Using ellipsometry and a quartz-crystal microbalance with dissipation (QCM-D), we obtained insight into the growth of the protein adsorption layer. Importantly, we found that phase transitions at the substrate can be triggered by certain interface properties, whether they exist in the bulk solution or not. Through the use of a hydrophilic, negatively charged surface (native silica), the direct binding of anions to the interface was prevented. Interestingly, this led to re-entrant adsorption even in the absence of re-entrant condensation in bulk. However, the overall amount of adsorbed protein was enhanced through stronger attractive protein-protein interactions in the presence of iodide salts. These findings illustrate how carefully chosen surface properties and salts can directly steer the binding of anions and cations, which guide protein behavior, thus paving the way for specific/triggered protein-protein, protein-salt, and protein-surface interactions.
蛋白质无处不在，在从生物体到蛋白质微芯片的许多领域都发挥着关键作用。在人类中，血清白蛋白在异物反应中起着突出的作用，因为它是第一个与例如植入物或支架相互作用的蛋白质。在这项研究中，我们专注于盐（即不同的阳离子（Y、La）和阴离子（Cl、I））对牛血清白蛋白（BSA）的影响，从其整体行为以及电荷在固液界面上的蛋白质吸附作用的角度来看，以了解和控制潜在的分子机制和相互作用。这是我们小组努力深入了解多价离子存在下蛋白质-蛋白质和蛋白质-表面相互作用的一部分。在本体中，我们建立了两个新的相图，不仅发现了多价阳离子触发的相变，还发现了蛋白质行为对阴离子类型的依赖性。观察到蛋白质之间的吸引力相互作用从 Cl <NO <I 增加，导致碘化物防止再进入冷凝并在本体中促进液-液相分离。使用椭圆光度法和石英晶体微天平（QCM-D），我们深入了解了蛋白质吸附层的生长。重要的是，我们发现基质中的相变可以通过某些界面特性触发，无论它们是否存在于本体溶液中。通过使用亲水性、带负电荷的表面（天然二氧化硅），可以防止阴离子直接与界面结合。有趣的是，即使在本体中不存在再进入冷凝，这也导致再进入吸附。然而，在存在碘化物盐的情况下，通过更强的蛋白质-蛋白质吸引力相互作用，吸附的蛋白质总量增加。这些发现说明了如何通过精心选择的表面特性和盐可以直接引导阴离子和阳离子的结合，从而指导蛋白质行为，从而为特定/触发的蛋白质-蛋白质、蛋白质-盐和蛋白质-表面相互作用铺平道路。
