Acyl chain asymmetry and polyunsaturation of brain phospholipids facilitate membrane vesiculation without leakage

Abstract

Phospholipid membranes form cellular barriers but need to be flexible enough to divide by fission. Phospholipids generally contain a saturated fatty acid (FA) at position sn1 whereas the sn2-FA is saturated, monounsaturated or polyunsaturated. Our understanding of the impact of phospholipid unsaturation on membrane flexibility and fission is fragmentary. Here, we provide a comprehensive view of the effects of the FA profile of phospholipids on membrane vesiculation by dynamin and endophilin. Coupled to simulations, this analysis indicates that: (i) phospholipids with two polyunsaturated FAs make membranes prone to vesiculation but highly permeable; (ii) asymmetric sn1-saturated- sn2-polyunsaturated phospholipids provide a tradeoff between efficient membrane vesiculation and low membrane permeability; (iii) When incorporated into phospholipids, docosahexaenoic acid (DHA; omega-3) makes membranes more deformable than arachidonic acid (omega-6). These results suggest an explanation for the abundance of sn1-saturated- sn2-DHA phospholipids in synaptic membranes and for the importance of the omega-6/omega-3 ratio on neuronal functions.

eLife digest

Surrounding each living cell is a membrane that is mainly made of fat molecules called phospholipids. Similar membranes also surround many of the structures inside cells. It is important for life that these membranes are impermeable to many molecules; for example, they do not allow ions to cross them freely. The membranes also need to be flexible and allow cells to form different shapes. Flexible membranes also allow cells to move molecules around and to divide to produce new cells.

Each phospholipid includes two long chains of atoms called fatty acids. There are many fatty acids but they are typically grouped into saturated and unsaturated based on their chemical structures. The omega-3 and omega-6 fats are both groups of unsaturated fatty acids that are found in brain cells. Many phospholipids in cell membranes contain one saturated and one unsaturated fatty acid but it is not clear why.

By studying fat molecules in the laboratory and combining this with simulations, Manni et al. have now examined the effects of fatty acids on membranes. The investigation showed that phospholipids with both saturated and unsaturated fatty acids strike a balance between impermeable and flexible membranes. More unsaturated fatty acids make more flexible membranes but they are too permeable to be used in cells. The experiments also revealed that omega-3 unsaturated fats aid flexibility more than omega-6. This finding may help to explain why the relative amounts of omega-3 and -6 are so important in the membranes of brain cells.

The connection between the fats we eat and the fatty acids in our cells is complex. Yet, findings like these serve to remind us that we need a balanced diet of different fats to keep all our cells healthy.