CPM Seminar

Hybrid lipids promote the formation of nanoscale domains in membranes

Benoit Palmieri

McGill University & Weizmann Institute of Science

Cell membranes are composed of many kinds of lipids and other biological molecules. It has been hypothesized that the membrane bilayer in living cells can form stable domains (“lipid rafts”) of uniform composition and of sizes of the order of nanometers to tens of nanometers; larger than the individual lipid head groups but much smaller than the overall cell size. This behavior is important because rafts are believed to mediate cellular functions. Nanoscale domains have also been observed in simpler (inactive) model membranes such as giant unilamelar vesicles assembled with a controlled lipid composition. The mechanism which stabilizes such nanodomains is not understood, even in model membranes, and simple phase-separation arguments usually predict macroscopic domains. We proposed a ternary mixture model to describe the phase behavior of model membranes comprising saturated, unsaturated and line active hybrid lipids. The model is based on molecular chain-chain interactions where the packing incompatibility between “straight” saturated chain and “kinked” unsaturated chains favors macroscopic phase separation. The hybrid lipid is a naturally occurring linactant, it has one chain of both types and it can reduce the packing incompatibility between domains of saturated and unsaturated lipids by residing at their boundary. The model allows the prediction of domain structures for arbitrary hybrid composition and includes the dependence of the interactions of the hybrid lipids on their orientations in a simple way. In the single phase, mixed regime, the theory predicts fluctuations domains of characteristic length scales and time scales that are, respectively, shorter and longer when hybrid lipids are added. Nanoscale fluctuation domains similar to lipid rafts are more probable and have longer lifetimes. In the phase separated, coexistence regime, a variational principle is used to calculate the energy associated with the presence of the interface separating bulk phases rich in saturated/unsaturated lipids. At large hybrid fractions, the theory predicts that zero line tension can be achieved close to room temperature; in a regime that may be physiologically relevant. Under these conditions, the membrane can spontaneously form more interfaces and promote the formation of small (nano) and stable domains. Connections with recent experiments that focus on the phase behavior of model membrane and ideas for further theoretical development (i.e. spontaneous splay induced by hybrid lipids, explicit dependence on lipid chain order) will be discussed.

References:
Robert C. Brewster, P.A. Pincus and Samuel A. Safran, Biophys J., 97, 1087 (2009).
Benoit Palmieri and Samuel A. Safran, Langmuir, 29, 5246 (2013).
Benoit Palmieri and Samuel A. Safran, Phys. Rev. E, 88, 032708 (2013).
B. Palmieri, Tetsuya Yamamoto, Robert C. Brewster and Samuel A. Safran, Adv. Colloid Interface Sci., 208, 58 (2014).