Phosphatidic Acid - Biophysical Properties of PA

Biophysical Properties of PA

PA is a unique phospholipid in that it has a small highly-charged head group that is very close to the glycerol backbone. PA is known to play roles in both vesicle fission and fusion, and these roles may relate to the biophysical properties of PA.

At sites of membrane budding or fusion, the membrane becomes or is highly curved. A major event in the budding of vesicles, such as transport carriers from the Golgi, is the creation and subsequent narrowing of the membrane neck. Studies have suggested that this process may be lipid-driven, and have postulated a central role for DAG due to its, likewise, unique molecular shape. The presence of two acyl chains but no headgroup results in a large negative curvature in membranes.

The LPAAT BARS-50 has also been implicated in budding from the Golgi. This suggests that the conversion of lysoPA into PA might affect membrane curvature. LPAAT activity doubles the number of acyl chains, greatly increasing the cross-sectional area of the lipid that lies ‘within’ the membrane while the surface headgroup remains unchanged. This can result in a more negative membrane curvature. Researchers from Utrecht University have looked at the effect of lysoPA versus PA on membrane curvature by measuring the effect these have on the transition temperature of PE from lipid bilayers to nonlamellar phases using 31P-NMR. The curvature induced by these lipids was shown to be dependent not only on the structure of lsyoPA versus PA but also on dynamic properties, such as the hydration of head groups and inter- and intramolecular interactions. For instance, Ca2+ may interact with two PAs to form a neutral but highly-curved complex. The neutralisation of the otherwise repulsive charges of the headgroups and the absence of any steric hindrance enables strong intermolecular interactions between the acyl chains, resulting in PA-rich microdomains. Thus in vitro, physiological changes in pH, temperature, and cation concentrations have strong effects on the membrane curvature induced by PA and lysoPA. The interconversion of lysoPA, PA, and DAG - and changes in pH and cation concentration - can cause membrane bending and destabilisation, playing a direct role in membrane fission simply by virtue of their biophysical properties. However, though PA and lysoPA have been shown to affect membrane curvature in vitro; their role in vivo is unclear.

The roles of lysoPA, PA, and DAG in promoting membrane curvature do not preclude a role in recruiting proteins to the membrane. For instance, the Ca2+ requirement for the fusion of complex liposomes is not greatly affected by the addition of annexin I, though it is reduced by PLD. However, with annexin I and PLD, the extent of fusion is greatly enhanced, and the Ca2+ requirement is reduced almost 1000-fold to near physiological levels.

Thus the metabolic, biophysical, recruitment, and signaling roles of PA may be interrelated.