A Model for the Lipid Pretransition: Coupling of Ripple Formation with the Chain-Melting Transition

Abstract

Below the thermotropic chain-melting transition, lipid membrane c(P) traces display a transition of low enthalpy called the lipid pretransition. It is linked to the formation of periodic membrane ripples. In the literature, these two transitions are usually regarded as independent events. Here, we present a model that is based on the assumption that both pretransition and main transition are caused by the same physical effect, namely chain melting. The splitting of the melting process into two peaks is found to be a consequence of the coupling of structural changes and chain-melting events. On the basis of this concept, we performed Monte Carlo simulations using two coupled monolayer lattices. In this calculation, ripples are considered to be one-dimensional defects of fluid lipid molecules. Because lipids change their area by approximately 24% upon melting, line defects are the only ones that are topologically possible in a triangular lattice. The formation of a fluid line defect on one monolayer leads to a local bending of the membrane. Geometric constraints result in the formation of periodic patterns of gel and fluid domains. This model, for the first time, is able to predict heat capacity profiles, which are comparable to the experimental c(P) traces that we obtained using calorimetry. The basic assumptions are in agreement with a large number of experimental observations.

On soliton propagation in biomembranes and nerves

“…The bending elasticity of membranes is related to their lateral compressibility (21). The elasticity changes predicted from heat capacity profiles are identical to those found in experiments (7,8). The heat capacity, lateral density, and isothermal and isentropic lateral compressibilities for unilamellar DPPC vesicles and lung surfactant are given in Fig.…”

“…It was found experimentally that the excess enthalpy, ⌬H, excess volume change, ⌬V, and excess area change, ⌬A, of the lipid melting transitions obey the relation ⌬V(T) ϭ ␥ V ⌬H(T) (2, 3) and, more indirectly, that ⌬A(T) ϭ ␥ A ⌬H(T) (2,7,8). The constants ␥ V ϭ 7.8 ϫ 10 Ϫ4 cm 3 ͞J and ␥ A ϭ 8.9 ϫ 10 3 cm 2 ͞J, which are identical within experimental error for various phosphatidylcholines, lipid mixtures, lung surfactant, and E. coli membranes (3).…”

“…It has been suggested on theoretical and experimental grounds that these response functions are all simple functions of the heat capacity (2)(3)(4). The sound velocities of lipid dispersions obtained with ultrasonic measurements and the bending elasticities of giant vesicles are practically identical to the profiles calculated from the heat capacity (5)(6)(7)(8). Within certain limits, it is thus possible to calculate the response functions from the heat capacity without detailed knowledge of the composition of the lipid mixture.…”

Drug permeability across a phospholipid vesicle based barrier: 3. Characterization of drug–membrane interactions and the effect of agitation on the barrier integrity and on the permeability

“…The pretransition is less cooperative than the main transition. The occurrence of the pretransition is dependent on the type of head group of the phospholipids in the bilayer, it also seems to be dependent on the lamellarity of the liposomes (Heimburg, 2000). The shift in the Tpre towards lower temperatures upon addition of drug compounds indicates a molecular interaction between the head group of the phospholipid and the drugs.…”

“…The pretransition is generally acknowledged to be a consequence of fluid lipid line defects, i.e. formation of periodic ripples in the membrane surface that appear between the pretransition temperature (Tpre) and the main transition temperature (Tm) (Beni et al, 2006;Heimburg, 2000;Janiak et al, 1976). The pretransition is less cooperative than the main transition.…”