We here report on flavonols (myricetin (MCE) and its glycoside myricitrin (MCI)) – 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) membrane interactions focusing on the effects of flavonol clustering on the membrane thermotropic and nanomechanical properties.

Atomic force microscopy (AFM), force spectroscopy (FS) and differential scanning calorimetry (DSC) together with molecular dynamics (MD) simulations provided a consistent picture of flavonol - DMPC membrane interactions. DMPC membrane as a supported lipid bilayer preserved its integrity even at higher flavonol molar fraction x. When present at x = 0.1 – 0.3, MCE and MCI both slightly improve DMPC bilayer fluidity which is evidenced by the decrease in the main phase transition temperature T_m. MCE is found within the interior of the bilayer, while MCI incorporates in the head group-water interface region. AFM and FS confirmed clusters as protrusions with an average height of 0.012 μm and average diameters of 0.60 and 0.24 μm for MCE and MCI clusters, respectively. The average membrane thickness in DMPC fluid phase decreases for 7% at x_MCE = 0.30, while only 4% at x_MCI = 0.27.

The induced membrane changes are dependent on the chemical and physical properties of inserted flavonols. The hypothesis regarding the tendency of flavonol to clustering in membranes by increasing flavonol molar fraction has been confirmed.