Bergamottin: location, aggregation and interaction with the plasma membrane

Abstract

Bioactive furanocoumarins, a group of natural secondary metabolites common in higher plants, are recognized for their benefits to human health and have been shown to have numerous biological properties. However, the knowledge of its biomolecular mechanism is not known. One of the main furanocoumarins is bergamottin (BGM), which is characterized by a planar three-ringed structure and a hydrocarbon chain, which give BGM its high lipid/water partition coefficient. Because of that, and although the biological mechanism of BGM is not known, BGM bioactive properties could be ascribed to its potential to interact with the biological membrane, modulating its structure, changing its dynamics and at the same time that it might interact with lipids. For our goal, we have applied molecular dynamics to determine the position of BGM in a complex membrane and discern the possibility of certain interactions with membrane lipids. Our findings establish that BGM tends to locate in the middle of the hydrocarbon layer of the membrane, inserts in between the hydrocarbon chains of the phospholipids in an oblique position with respect to the membrane plane, increasing the fluidity of the membrane. Significantly, BGM tends to be surrounded by POPC molecules but exclude the molecule of CHOL. Outstandingly, BGM molecules associate spontaneously creating aggregates, which does not preclude them from interacting with and inserting into the membrane. The bioactive properties of BGM could be ascribed to its membranotropic effects and support the improvement of these molecules as therapeutic molecules, giving place to new opportunities for potential medical improvements.

Communicated by Ramaswamy H. Sarma

Keywords:

• Bergamottin
• plasma membrane
• molecular dynamics
• membrane interaction

Acknowledgements

NAMD was developed by the Theoretical and Computational Biophysics Group in the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign. We are very grateful to SIPT, Universitas Miguel Hernández (UMH), for the generous use of the UMH Computer Cluster. This work was not funded by any external or internal funding agencies.

Disclosure statement

No potential conflict of interest was reported by the author(s).