Elucidating the Dynamic Interactions of Borrelia burgdorferi Surface Proteins with Fibronectin using Atomic Force Microscopy

Lyme disease (LD) is the most prevalent arthropod-borne illness in the United States, with an estimated 476,000 cases diagnosed annually. Borrelia burgdorferi (Bb), the primary causative agent of LD in the northern U.S., is a bacterium with a genome rich in adhesins, which may allow it to colonize extracellular matrix-rich tissues as a potential mechanism for immune evasion. In this study, we examined the mechanical interactions between six Bb proteins—RevA, BmpA, OspA, FlaB, OspC, and BBK32—and the human protein fibronectin (Fn) using Atomic Force Microscopy (AFM). Dishes were coated with the target proteins, while cantilever tips were functionalized with Fn for Dynamic Force Spectroscopy (DFS) measurements at the single-molecule level. This approach enabled us to quantify the dynamic force interactions of these adhesins under varying loading rates, providing detailed insights into their biomechanical properties. The aim of this study is to better understand the role of surface proteins in the pathogenesis of Lyme disease, their mechanisms of action, and their potential as targets for therapeutic development.