Interaction between amphiphilic drugs and biofilms revealed by surface-enhanced Raman spectroscopy

This study adopted surface-enhanced Raman scattering (SERS) to assess membrane lipid order and to disclose structure-dependent differential interaction mechanisms between drug molecules and cell membranes by constructing lipid-coated metal nanoparticle conjugates. A dipalmitoyl phosphatidylcholine (DPPC)/cholesterol membrane model was first built to mimic the cell membrane. Based on the ratio of lipid-related characteristic peaks (I₂₈₇₇/I₂₈₄₈), lateral interaction order parameters (Slat) were obtained and used to systematically investigate the regulatory effects of cholesterol and statins on the physical properties of cell membranes. S_lat initially increases and then decreases with increasing cholesterol content, confirming its reliability as an indicator of membrane lipid order. Next, three statin drugs (simvastatin, lovastatin, and pravastatin) were applied to these biomimetic composite membranes. We found that these drugs disrupted the order of the model membrane, as evidenced by a decrease in Sₗₐₜ, revealing structure-dependent differential interaction mechanisms between drugs and membranes. Furthermore, this method was applied to the extracted cell membranes of MCF-7 and MCF-10A cells. Due to differences in cholesterol content between the two cell membrane types, Sₗₐₜ could be used to effectively distinguish cancer cells from normal cells. Furthermore, the results regarding the interactions between statins and native cell membranes are consistent with those obtained from biomimetic membranes. Simvastatin treatment exacerbated the disorder of membranes. This work introduces a unique technical tool for membrane biophysics research and offers novel insights into the design of anticancer and antibacterial strategies through targeted regulation of membrane lipid order.