We demonstrate that a molten globule‐like (MG) state of a protein, usually described as a compact yet non‐folded conformation that is only present in a narrow and delicate parameter range, is preserved in the high concentration environment of the protein hydrogel. We reveal mainly by means of electron paramagnetic resonance (EPR) spectroscopy that bovine serum albumin (BSA) retains the known basic MG state after a hydrogel has been formed from 20 wt% precursor solutions. At pH values of ~11.4, BSA hydrogels made from MG‐BSA remain stable for weeks, while gels formed at slightly different (~0.2) pH units above and below the MG‐state value dissolve into viscous solutions. On the contrary, when hydrophobic screening agents are added such as amphiphilic, EPR‐active stearic acid derivatives (16‐DOXYL‐stearic acid, 16‐DSA), the MG‐state based hydrogel is the least long‐lived, as the hydrophobic interaction of delicately exposed hydrophobic patches of BSA molecules is screened by the amphiphilic molecules. These bio‐ and polymer‐physically unexpected findings may lead to new bio‐compatible MG‐based hydrogels that display novel properties in comparison to conventional gels.

中文翻译：

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血清白蛋白的水凝胶呈熔融球状

我们证明了蛋白质的熔融球状（MG）状态（通常被描述为仅存在于狭窄且细腻的参数范围内的紧凑而未折叠的构象）在蛋白质水凝胶的高浓度环境中得以保留。我们主要通过电子顺磁共振（EPR）光谱揭示，在由20 wt％的前体溶液形成水凝胶后，牛血清白蛋白（BSA）保留了已知的基本MG状态。在〜11.4的pH值下，由MG-BSA制成的BSA水凝胶保持稳定数周，而在MG-状态值之上和之下的pH单位略有不同（〜0.2）形成的凝胶则溶解成粘性溶液。相反，当添加疏水性屏蔽剂（例如两亲性，EPR活性的硬脂酸衍生物（16-DOXYL-硬脂酸，16-DSA））时，基于MG态的水凝胶寿命最短，因为两亲分子可筛选出微妙暴露的BSA分子疏水片的疏水相互作用。这些生物和聚合物物理上出乎意料的发现可能会导致新的生物相容性基于MG的水凝胶与传统凝胶相比具有新颖的性能。