Label-Free Plasmon-Waveguide Resonance Analysis of Mucin Network Remodeling by Cationic Polymers

Surface plasmon resonance (SPR) quantifies biomolecular interactions using p-polarization. Plasmon-waveguide resonance (PWR) adds s-polarization, yielding concurrent readouts of refractive-index changes perpendicular and parallel to interfacial films and, thus, optical anisotropy. We validated label-free PWR for mucin and quantified how cationic polymers remodel immobilized anionic mucin via a graphical mass/structure decomposition. Reproducible system performance was confirmed with air, water, and PBS; mucin showed concentration-dependent angle shifts with the expected order air < water < PBS < mucin in both polarizations. A sensitivity factor (Sf = Δs/Δp) of 0.33 from buffer transitions enabled the resolution of mass versus structural contributions. Mucin (0.1% w/v) was probed with chitosan, branched polyethylenimine (PEI), and poly-l -lysine (PLL) (each 0.1% w/v), with baseline mucin responses being mass dominated (∼77%) with a smaller structural component (∼23%). PEI produced large positive shifts (Δp = 310.3 ± 56.8; Δs = 300.2 ± 54.8 millidegrees), yielding a mass-dominated response (∼65%) with a substantial structural term (∼35%) oriented toward increased anisotropy relative to mucin, consistent with strong polymer accumulation on the mucin film. Chitosan caused a moderate increase in Δp (82.3 ± 40.4) with negligible Δs (11.2 ± 7.4 millidegrees), producing a smaller mass contribution relative to PEI and a notable structural contribution (∼38%); the vector orientation indicates decreased anisotropy with moderate mass addition. In contrast, PLL induced negative shifts (Δp = -101.6 ± 15.6; Δs = -31.1 ± 23.8 millidegrees), reflecting net mass loss with a minor structural component (∼14%), consistent with partial mucin desorption/thinning. Dual-polarization PWR thus resolves polymer-specific outcomes, including decreased anisotropy with mucoadhesive restructuring (chitosan), mass-dominant accumulation with increased anisotropy (PEI), and barrier weakening via partial desorption (PLL). Mucin-coated PWR provides a reproducible, label-free platform to deconvolve mass versus structural effects in mucin-polymer interactions and to rapidly screen mucoadhesive and penetration-enhancing excipients for mucosal drug delivery.