Statistical analysis of virion-cell interactions mediated by peptide nanofibrils and peptide amphiphiles using STEM tomography

2026-04-30

AI Summary

This study addresses the current lack of quantitative understanding regarding how peptide nanofibers and peptide amphiphiles modulate virus–cell interactions. We establish a comprehensive framework based on scanning transmission electron microscopy (STEM) tomography for data acquisition, processing, and statistical analysis, introducing geometric descriptors to objectively quantify the spatial distribution of viral particles under peptide mediation and their relative positioning with respect to cells. Our results demonstrate that all four tested peptides efficiently capture viruses and substantially reduce free virions, yet they exhibit distinct spatial confinement patterns that correlate strongly with their respective transduction-enhancing efficacies. This approach provides a generalizable, quantitative paradigm for evaluating infection-enhancing nanomaterials.

Abstract

Peptide nanofibrils (PNFs) and peptide amphiphiles (PAs) are promising tools for enhancing viral transduction and gene transfer. However, quantitative insight into how their supramolecular architecture governs virion-cell interactions is limited. Here, we introduce a framework for the acquisition, processing, and statistical analysis of scanning transmission electron microscopy (STEM) tomograms to objectively quantify peptide-virion-cell interactions. Using four transduction-enhancing peptides (D4, Vectofusin-1, palmitic acid-PA (pal-PA), and eicosapentaenoic-PA (eic-PA)), peptide aggregate morphology, interfacial contact areas, and the spatial organization of virions with respect to peptides and cells were analyzed using advanced geometric descriptors. All peptides efficiently captured virions, resulting in few free virions, but they differ in how strictly virions were spatially confined near the cell surface. These differences reflect alternative spatial organization strategies, which are likely crucial factors influencing transduction-enhancing efficacy. Our approach provides a novel, generalizable method to evaluate infection-enhancing nanomaterials and guides the rational design of next-generation peptide assemblies for therapeutic viral delivery.

Problem

• virion-cell interactions
• peptide nanofibrils
• peptide amphiphiles
• supramolecular architecture
• viral transduction

Innovation

• STEM tomography
• peptide nanofibrils
• peptide amphiphiles
• virion-cell interactions
• geometric descriptors