Biology subjects

Angioletti-Uberti, S.

Publications and source records attributed to Angioletti-Uberti, S..

3 recordsLinked to original sources

bioRxiv2024

Self-reactive B cells traverse a perfect storm of somatic mutagenesis to cause a virus-induced autoimmune disease

The unexplained association between infection and autoimmune disease is strongest for hepatitis C virus-induced cryoglobulinemic vasculitis (HCV-CV). We traced the evolution of the pathogenic rheumatoid factor (RhF) autoantibodies in four HCV-CV patients by deep single cell multi-omic analysis, revealing three sources of B cell somatic mutation converged to drive accumulation of a large disease causing clone. A sensitive method for quantifying low affinity binding revealed three recurring heavy/light chain combinations created by V(D)J recombination bound self IgG but not viral E2 antigen. Whole genome sequencing revealed accumulation of thousands of somatic mutations, at levels comparable to CLL and normal memory B cells, but with 1-2 corresponding to driver mutations found recurrently in B cell leukemia/lymphoma. V(D)J hypermutation created autoantibodies with compromised solubility. In this virus-induced autoimmune disease, infection promotes a perfect storm of somatic mutagenesis in the descendants of a single B cell.

immunology↗

bioRxiv2023

Valency of Ligand-Receptor Binding Ignored by Pair Potentials

Molecular dynamics simulations have been crucial for investigating the dynamics of nanoparticle uptake by cell membranes via ligand-receptor interactions. Use of coarsegrained models has enabled evaluation of the effects of nanoparticle size, shape, ligand distribution on nanoparticles surface, or used thoroughly in the past decade, where a percentage of lipid heads, receptors, are attracted to sites on the nanoparticle surface, ligands. However, when pair-potentials are used to represent ligand-receptor interactions, the number of receptors interacting with one ligand, valency, may vary. We demonstrate that the curvature of a nanoparticle, strength of ligand-receptor interactions, and ligand or receptor concentration change the valency - ranging from 3.4 to 5.1 in this study. Such change in valency can create inaccurate comparisons between nanoparticles, or even result in the uptake of smaller nanoparticles than would be expected. To rectify this inconsistency we propose the adoption of a model based on bond-formation and use it to determine the extent to which previous studies may have been effected. This work recommends avoiding pair-potentials for modeling ligandreceptor interactions to ensure methodological consistency in nanoparticle studies. TOC GraphicA rendering of a ligand coated nanoparticle coming into contact with a lipid bilayer membrane. The receptor in the membrane is highlighted for clarity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/557452v3_ufig1.gif" ALT="Figure 1"> View larger version (63K): org.highwire.dtl.DTLVardef@10730a2org.highwire.dtl.DTLVardef@109f0b9org.highwire.dtl.DTLVardef@19b0d80org.highwire.dtl.DTLVardef@93557a_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2022

Nanoscale Friction of Model Hair Surfaces

We investigate the nanoscale friction between biomimetic hair surfaces using chemical colloidal probe atomic force microscopy experiments and nonequilibrium molecular dynamics simulations. In the experiments, friction is measured between water-lubricated silica surfaces functionalised with monolayers of either octadecyl or sulfonate groups, which are representative of the surfaces of virgin and ultimately bleached hair, respectively. In the simulations, friction is monitored between coarse-grained model hair surfaces with different levels of chemical damage, where different fractions of grafted lipid molecules are randomly replaced with sulfonate groups. The sliding velocity dependence of friction can be described using an extended stress-augmented thermally activation model. As the damage level increases, the friction generally increases, but its sliding velocity-dependence decreases. At low sliding speeds, which are closer to those encountered physiologically and experimentally, we observe a monotonic increase of friction with the damage ratio, which is consistent with our new experiments using biomimetic surfaces and previous ones using real hair. This observation demonstrates that modified surface chemistry, rather than roughness changes or subsurface damage, control the increase in nanoscale friction of damaged hair. We expect the experimental and computational model surfaces proposed here to be useful to screen the tribological performance of hair care formulations.

biochemistry↗