Polyunsaturated Phospholipids Increase Cell Resilience to Mechanical Constraints

Despite the fact that PolyUnsaturated Fatty Acids (PUFA) are generally accepted to be good for health, the mechanisms of their bona fide benefits still remain elusive. PUFA are particularly enriched in the membrane Phospholipids (PLs) of selective organs, among which skeletal muscles and the cardiovascular system are prime examples. The fatty acid composition of PLs is known to regulate crucial membrane properties, including rigidity, elasticity and plasticity. Since muscle cells undergo repeated cycles of elongation and relaxation and are constantly exposed to mechanical stress, we postulated in the present study that PUFA-containing PLs could be central players for muscle cell adaptation to mechanical constraints. By a combination of in cellulo and in silico approaches, we show that PUFA, and particularly the ω-3 DocoHexaenoic Acid (DHA), regulate important properties of the plasma membrane that improve muscle cell resilience to mechanical constraints. Thanks to their unique property to contortionate within the bilayer plane, they facilitate the formation of Vacuole-like dilation (VLD) which, in turn, reduce membrane stress and avoid cell breakage under mechanical constraints.