Serum albumin has shown great potential in the development of new biomaterials for drug delivery systems. Different methods have been proposed to synthesis hydrogels out of serum albumin. It has been observed that ethanol can also act as a trigger for serum albumin denaturation and subsequent gelation. In this study, we focus on basic mechanisms of the albumin gelation process at 37 °C when using the chemical denaturant ethanol. The temperature of 37 °C was chosen to resemble human body temperature, and as under physiological conditions, albumin is in a non-denatured N conformation. As established in our previous publication for the triggers of pH and temperature (and time), we here explore the conformational and physical properties space of albumin hydrogels when they are ethanol-induced and show that the use of ethanol can be advisable for certain gel properties on the nanoscopic and macroscopic scale. To this end, we combine spectroscopic and mechanically (rheology) based data for characterizing the gels. We also study the gels′ binding capacities for fatty acids with electron paramagnetic resonance (EPR) spectroscopy, which implies observing the effects of bound stearic acids on gelation. Ethanol reduces the fraction of the strongly bound FAs in bovine serum albumin (BSA) hydrogels up to 52% and induces BSA hydrogels with a maximum storage modulus of 5000 Pa. The loosely bound FAs in ethanol-based hydrogels, besides their relatively weak mechanical properties, introduce interesting new materials for fast drug delivery systems and beyond.

Neurodegenerative disorders are among the most common diseases in modern society. However, the molecular bases of diseases such as multiple sclerosis or Charcot−Marie−Tooth disease remain far from being fully understood. Research in this field is limited by the complex nature of native myelin and by difficulties in obtaining good in vitro model systems of myelin. Here, we introduce an easy-to-use model system of the myelin sheath that can be used to study myelin proteins in a native-like yet well-controlled environment. To this end, we present myelin-mimicking nanodiscs prepared through one of the amphiphilic copolymers styrene/maleic acid (SMA), diisobutylene/maleic acid (DIBMA), and styrene/maleimide sulfobetaine (SMA-SB). These nanodiscs were tested for their lipid composition using chromatographic (HPLC) and mass spectrometric (MS) methods and, utilizing spin probes within the nanodisc, their comparability with liposomes was studied. In addition, their binding behavior with bovine myelin basic protein (MBP) was scrutinized to ensure that the nanodiscs represent a suitable model system of myelin. Our results suggest that both SMA and SMA-SB are able to solubilize the myelin-like (cytoplasmic) liposomes without preferences for specific lipid headgroups or fatty acyl chains. In nanodiscs of both SMA and SMA-SB (called SMA(-SB)-lipid particles, short SMALPs or SMA-SBLPs, respectively), the polymers restrict the lipids' motion in the hydrophobic center of the bilayer. The headgroups of the lipids, however, are sterically less hindered in nanodiscs when compared with liposomes. Myelin-like SMALPs are able to bind bovine MBP, which can stack the lipid bilayers like in native myelin, showing the usability of these simple, well-controlled systems in further studies of protein−lipid interactions of native myelin.

Here, we for the first time establish nanodiscs with the challenging lipid composition of myelin of the peripheral or central nervous systems, respectively (PNS and CNS, both containing >40% cholesterol, which so far has been thought to be detrimental for nanodisc formation).Thus, we prove that more complex lipid model membrane systems are in general accessible through nanodiscs and can study protein-lipid interactions in myelin and factors driving myelin formation or degradation using combinations of myelin proteins in a highly controlled lipid environment resembling myelin’s cytoplasmic leaflet. For the functional studies, initial proof-of-principle experiments using myelin basic protein have been performed. <br>