The interaction of viruses with cells is mediated by the glycocalyx, a ubiquitous cell coating layer. Here, we present a study of the effects of the cellular glycocalyx, a complex outer cell structure, on viral internalization. Using both simulations and experiments, we have shown that the structure of the glycocalyx, specifically the number of cross-links within it, can greatly influence the ability of a virus to infect a cell. We show that the presence of the glycocalyx plays a direct role in viral internalization, and targeting the glycocalyx can be a potential avenue for future therapies. Overall, by comparison with experimental results, we conclude that a brush-like glycocalyx model is the more appropriate computational model compared to its partially cross-linked versions.

The Ebola virus is a deadly pathogen that has been threatening public health for decades. Recent studies have revealed alternative viral invasion routes where Ebola virus approaches cells via interactions among phosphatidylserine (PS), PS binding ligands such as Gas6, and TAM family receptors such as Axl. In this study, we investigate the interactions among phosphatidylserine on the Ebola viral-like particle (VLP) membrane, human Gas6, and human Axl using atomic force microscope-based single molecule force spectroscopy to compare their binding strength and affinity from a biomechanical perspective. The impact of calcium ions on their interactions is also studied and quantified to provide more details on the calcium-dependent phosphatidylserine-Gas6 binding mechanism. Our results indicate that, in the presence of calcium ions, the binding strengths of VLP-Gas6 and VLP-Gas6-Axl increase but are still weaker than that of Gas6-Axl, and the binding affinity of VLP-Gas6 and VLP-Gas6-Axl is largely improved. The binding strength and affinity of Gas6-Axl basically remain the same, indicating no impact in the presence of calcium ions. Together, our study suggests that, under physiological conditions with calcium present, the Ebola virus can utilize its membrane phosphatidylserine to dock on cell surface via Gas6-Axl bound complex.

Von Willebrand Factor (VWF) plays a crucial role in hemostasis and thrombosis, with its A1 and A2 domains being keys to its function. This study investigates the impact of the vicinal disulfide bond in the A2 domain on the interaction between the A1 domain and platelet glycoprotein Ibα (GPIbα). Using single-molecule optical tweezers, we evaluated the mechanical unfolding and refolding behaviors of wild-type A2 (WT A2) and an A2 mutant without the vicinal disulfide bond (CC-AA A2). Our results reveal that CC-AA A2 exhibits heterogeneous unfolding patterns and altered refolding characteristics compared to WT A2. Furthermore, microscale thermophoresis and AlphaFold3 predictions demonstrate enhanced binding affinity of CC-AA A2 to the A1 domain and decreased binding affinity of CC-AA A1A2 to the ligand binding domain (LBD) of GPIbα. These findings advance our understanding of the regulatory role of the vicinal disulfide bond in VWF function and its potential implications in hemostasis and thrombosis.