**5. Conclusions**

Our results indicate that resveratrol interacts with zwitterionic and neutral PLMs, by incorporating into PLMs and forming transient conductive units, whereas it is unable to interact with DOPE:DOPS PLMs. In light of this, we hypothesize a model in which its fundamental steps are: (1) adsorption of resveratrol onto the membrane surface. This step is common to the neutral PLMs and to the negatively-charged PLMs used in this study; and (2) in neutral PLMs, formation of transient conductive units made up of molecules of resveratrol oriented with their long axis along the membrane normal and assembled together (Figure 6). The incorporation and channel-like events formation indicate that resveratrol is located in the hydrophobic core of the bilayer. These results, obtained by simultaneously monitoring membrane conductance and capacitance, may help to clarify the mechanism of action by which resveratrol performs its beneficial effects on human health, such as its antioxidant or anti-microbial properties and its scavenging of lipid radicals.

**Figure 6.** Schematic model of the resveratrol interaction with PLM at different lipid composition. Resveratrol adsorbs onto the membrane surface, regardless to the PLM composition. In POPC or POPC:Ch PLMs (top), resveratrol inserts and assembles into membrane forming conductive units, once an appropriate resveratrol/lipid ratio has been reached. In DOPE:DOPS PLMs (bottom), resveratrol inducing negative curvature of membrane is unable to insert into it.

> **Funding:** This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

> **Acknowledgments:** The authors acknowledge Anthony Green for proofreading and providing linguistic advice.

**Conflicts of Interest:** The author declares no conflict of interest.
