THEORETICAL STUDY OF THE ANTITUMORAL LIPID OHMLINE: SELF INTERACTION AND INCORPORATION INTO MEMBRANES

VALLI, FLORENCIA; HERRERA, FERNANDO E.

Ciudad Autónoma de Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argentina de Investigación Clínica (SAIC), entre otras.

The dysregulation of ion channel activity/expression emerged as acommon feature of cancer cells and the modulation of overexpressedion channels opens new perspectives in cancer therapy. Specifically,the SK3 channel is overexpressed in metastatic cells and Ohmline(1-O-hexadecyl-2-O-methyl-sn-glycero-3-lactose, Ohm) is an etherlipid that has been shown to reduce its activity and the migration capacityof cancer cells after incorporation into the plasma membrane.In this work, molecular dynamics simulations were used to studythe behavior of Ohm in aqueous solution and its incorporation intomodels of the plasma membrane and a membrane nanodomain.The simulated system were: i) The Ohmline system, it consist onseveral Ohm molecules in solution, ii) The plasma membrane system,similar to a cell membrane in composition, formed by POPC inone monolayer and POPE and POPS in the other monolayer and iii)The nanodomain system, similar to a membrane RAFT in composition,formed by a mixed of DSPC, sphingomyelin and cholesterol (itis supposed that SK3 channel is located into these nanodomains).Specifically, system ii) and iii) were studied in contact with dilutesolutions of Ohm molecules.The results have shown the ability of the Ohm molecule to form akind of micellar or fibrillar structures in solution, a fact that was alsoconfirmed by electron microscopy. The analysis of the incorporationof the Ohm molecule into systems ii) and iii), demonstrate theability of Ohm to be absorbed independently of the membrane composition,with similar mechanism. Some structural properties doesnot change upon incorporation, nevertheless, dynamical propertiessuch as the lateral diffusion is increased only in the raft system.These results allow us to infer that Ohm could induce fluidity in rigidmembranes such as the rigid nanodomains, affecting the packing ofthe lipids and in turn, reducing the activity of the SK3 ion channel.