How do oxidized polyunsaturated lipids asymmetrically found on one bilayer's leaflet affect cell membranes?

• Grant number: 24/14296-3
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2024
• End date: September 30, 2029
• Field of knowledge: Physical Sciences and Mathematics - Physics
• Principal Investigator: Thais Azevedo Enoki Liarte
• Grantee: Thais Azevedo Enoki Liarte
• Host Institution: Instituto de Física (IF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Mauricio da Silva Baptista ; Rosangela Itri

Abstract

We will create in vitro models for cell membranes and engineer lipid bilayers, with each leaflet having a distinct lipid composition yet coupled as a bilayer. The proposed leaflet compositions are designed to emulate the structural characteristics of the exoplasmic and cytoplasmatic leaflets of the plasma membrane. We will use the hemifusion method to create these bilayers. In our model, one leaflet of these bilayers will be rich in polyunsaturated lipids. We will cause the oxidation of polyunsaturated lipids using exposure to high-energy UV light or photosensitizers, such as methylene blue. The structure of oxidized lipids, which are found only in one of the leaflets, will change. This change results in a significant increase in the area per lipid or modification in lipid intrinsic curvature. We will test how changes in the oxidized structure of lipids change membrane morphology and mechanical properties. We will quantify the changes in bilayer mechanical properties using the micropipette aspiration method. We propose that the changes in the oxidized lipids will force the membrane to bend, forming tubules. It has been observed that cancer cells exhibit such deformations. Interestingly, lipid oxidation is related to skin cancer. Our proposal can potentially answer how oxidized polyunsaturated lipids asymmetrically found on one bilayer's leaflet affect cell membranes. (AU)