The low-complexity domain of the RNA-binding protein FUS (FUS LC) mediates liquid−liquid phase separation (LLPS), but the interactions between the repetitive SYGQ-rich sequence of FUS LC that stabilize the liquid phase are not known in detail. By combining NMR and Raman spectroscopy, mutagenesis, and molecular simulation, we demonstrate that heterogeneous interactions involving all residue types underlie LLPS of human FUS LC. We find no evidence that FUS LC adopts conformations with traditional secondary structure elements in the condensed phase; rather, it maintains conformational heterogeneity. We show that hydrogen bonding, π/sp², and hydrophobic interactions all contribute to stabilizing LLPS of FUS LC. In addition to contributions from tyrosine residues, we find that glutamine residues also participate in contacts leading to LLPS of FUS LC. These results support a model in which FUS LC forms dynamic, multivalent interactions via multiple residue types and remains disordered in the densely packed liquid phase.

Graphene, an allotrope of carbon, consists of a single layer of carbon atoms with uniquely tuneable properties. As such, graphene-based materials (GBMs) have gained interest for tissue engineering applications. GBMs are often discussed in the context of how different physicochemical properties affect cell physiology, without explicitly considering the impact of adsorbed proteins. Establishing a relationship between graphene properties, adsorbed proteins, and cell response is necessary as these proteins provide the surface upon which cells attach and grow. This review highlights the molecular adsorption of proteins on different GBMs, protein structural changes, and the connection to cellular function.

Phase transitions are important to understand cell dynamics, and the maturation of liquid droplets is relevant to neurodegenerative disorders. We combined NMR and Raman spectroscopies with microscopy to follow, over a period of days to months, droplet maturation of the protein fused in sarcoma (FUS). Our study reveals that the surface of the droplets plays a critical role in this process, while RNA binding prevents it. The maturation kinetics are faster in an agarose-stabilized biphasic sample compared with a monophasic condensed sample, owing to the larger surface-to-volume ratio. In addition, Raman spectroscopy reports structural differences upon maturation between the inside and the surface of droplets, which is comprised of β-sheet content, as revealed by solid-state NMR. In agreement with these observations, a solid crust-like shell is observed at the surface using microaspiration. Ultimately, matured droplets were converted into fibrils involving the prion-like domain as well as the first RGG motif.

Excess storage of lipids in ectopic tissues, such as skeletal muscle, liver, and heart, seems to associate closely with metabolic abnormalities and cardiac disease. Intracellular lipid storage occurs in lipid droplets, which have gained attention as active organelles in cellular metabolism. Recent developments in high-resolution microscopy and microscopic spectroscopy have opened up new avenues to examine the physiology and biochemistry of intracellular lipids. The aim of this review is to give an overview of recent technical advances in microscopy, and its application for the visualization, identification, and quantification of intracellular lipids, with special focus to lipid droplets. In addition, we attempt to summarize the probes currently available for the visualization of lipids. The continuous development of lipid probes in combination with the rapid development of microscopic techniques can provide new insights in the role and dynamics of intracellular lipids. Moreover, in situ identification of intracellular lipids is now possible and promises to add a new dimensionality to analysis of lipid biochemistry, and its relation to (patho)physiology.

Methylammonium lead iodide perovskite is an outstanding semiconductor for photovoltaics. One of its intriguing peculiarities is that the band gap of this perovskite increases with increasing lattice temperature. Despite the presence of various thermally accessible phonon modes in this soft material, the understanding of how precisely these phonons affect macroscopic material properties and lead to the peculiar temperature dependence of the band gap has remained elusive. Here, we report a strong coupling of a single phonon mode at the frequency of ~ 1 THz to the optical band gap by monitoring the transient band edge absorption after ultrafast resonant THz phonon excitation. Excitation of the 1 THz phonon causes a blue shift of the band gap over the temperature range of 185 ~ 300 K. Our results uncover the mode-specific coupling between one phonon and the optical properties, which contributes to the temperature dependence of the gap in the tetragonal phase.