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The eye is a vital organ in the visual system, which is composed of transparent vascular tissue. αB-crystallin, a significant protein found in the lens, plays a crucial role in our understanding of lens diseases. Mutations in the αB-crystallin protein can cause lens diseases, such as cataracts and myopathy. However, the molecular mechanism underlying the R120G mutation is not fully understood. In this study, we utilized molecular dynamics simulations to illustrate, in atomic detail, how the R120G mutation leads to the aggregation of αB-crystallin and scattering of light in the lens. Our findings show that the R120G mutation alters the dynamic and structural properties of the αB-crystallin protein. Specifically, this mutation causes the angle of the hairpin at the C-terminal to increase from 80° to 150°, while reducing the distance between the hydrophobic patches around residues 10 and 44-55 from 1.5 nm to 1 nm. In addition, our results showed that the mutation could disrupt the IPI motif - β4/β8 interaction. The disruption of this interaction could affect the αB-crystallin oligomerization and the chaperone activity of αB-crystallin protein. The exposed hydrophobic area at the IPI motif - β4/β8 could become the primary site for interprotein interactions, which are responsible for large-scale aggregation. We have demonstrated that, in wild-type αB-crystallin protein, salt bridges R120 and D109, R107 and D80 are formed. However, in the case of the R120G mutation, the salt bridges R120 and R109 are disrupted, and a new salt bridge with a different pattern is formed. In our study, it has been found that all of the changes associated with the R120G mutation are located at the interface of chains A and B, which could impact the multimerization of the αB-crystallin. Previous research on the K92-E99 residue has shown that a salt bridge in the dimer I can reduce the chaperone activity of the protein. Furthermore, the salt bridges R120 and D109, as well as R107 and D80 in dimer II, induce changes in the hydrophobic envelope of β-sheets in the α-crystallin domain (ACD). These changes could have an impact on the multimerization of the αB-crystallin, leading to disruption of the oligomer structure and aggregation. Moreover, the changes in the αB-crystallin resulting from the R120G mutation can lead to faulty interactions with other proteins, which can cause the aggregation of αB-crystallin with other proteins, such as desmin. These findings may provide new insights into the development of treatments for lens diseases. Communicated by Ramaswamy H. Sarma

Microfluidics cell-based assays require strong cell-substrate adhesion for cell viability, proliferation, and differentiation. The intrinsic properties of PDMS, a commonly used polymer in microfluidics systems, regarding cell-substrate interactions have limited its application for microfluidics cell-based assays. Various attempts by previous researchers, such as chemical modification, plasma-treatment, and protein-coating of PDMS revealed some improvements. These strategies are often reversible, time-consuming, short-lived with either cell aggregates formation, not cost-effective as well as not user- and eco-friendly too. To address these challenges, cell-surface interaction has been tuned by the modification of PDMS doped with different biocompatible nanomaterials. Gold nanowires (AuNWs), superparamagnetic iron oxide nanoparticles (SPIONs), graphene oxide sheets (GO), and graphene quantum dot (GQD) have already been coupled to PDMS as an alternative biomaterial enabling easy and straightforward integration during microfluidic fabrication. The synthesized nanoparticles were characterized by corresponding methods. Physical cues of the nanostructured substrates such as Young&rsquo, s modulus, surface roughness, and nanotopology have been carried out using atomic force microscopy (AFM). Initial biocompatibility assessment of the nanocomposites using human amniotic mesenchymal stem cells (hAMSCs) showed comparable cell viabilities among all nanostructured PDMS composites. Finally, osteogenic stem cell differentiation demonstrated an improved differentiation rate inside microfluidic devices. The results revealed that the presence of nanomaterials affected a 5- to 10-fold increase in surface roughness. In addition, the results showed enhancement of cell proliferation from 30% (pristine PDMS) to 85% (nano-modified scaffolds containing AuNWs and SPIONs), calcification from 60% (pristine PDMS) to 95% (PDMS/AuNWs), and cell surface marker expression from 40% in PDMS to 77% in SPION- and AuNWs-PDMS scaffolds at 14 day. Our results suggest that nanostructured composites have a very high potential for stem cell studies and future therapies.