Domain-Growth Kinetic Origin of Nonhorizontal Phase Coexistence Plateaux in Langmuir Monolayers: Compression Rigidity of a Raft-Like Lipid Distribution Laura R. Arriaga, † Iva ´n Lo ´pez-Montero, † Jordi Igne ´s-Mullol,* ,‡ and Francisco Monroy* ,† Mechanics of Biological Membranes and Biorheology, Departamento de Quı ´mica Fı ´sica I, UniVersidad Complutense de Madrid, 28040 Madrid, Spain, and Departamento de Quı ´mica Fı ´sica, UniVersidad de Barcelona, Martı ´ i Franque `s 1, 08028 Barcelona, Spain ReceiVed: December 16, 2009; ReVised Manuscript ReceiVed: February 15, 2010 The present work addresses the question of a nonhorizontal coexistence plateau found in the liquid-expanded (LE) to liquid-condensed (LC) transition of Langmuir monolayers of lipid amphiphiles, which is apparently incongruent with the first-order character of this main LE/LC phase transition. This pathology is understood in a mechanical context as a resistance of the monolayer against compression giving rise to a nonzero rigidity in the coexistence region. Surface rheology has allowed for a quantitative determination of the compression parameters, namely, dilational elasticity ε and viscosity η. Data for the phase coexistence region reveal dynamical stiffening at faster deformation, which points out a chief control of lipid diffusion on monolayer rigidity. Monolayer viscosity remains however low at the value corresponding to the continuous fluid phase. The presence of coexistence domains is then invoked as the structural element responsible for such a nontrivial rheology, the finite domain growth rate imposing a kinetic limit for equilibrium compression along a quasi- static path. Brewster angle microscopy has allowed for studying the kinetic mechanism for domain growth. The finite rigidity observed at the coexistence region is related to the resistance of LC domains to grow at the expense of the LE phase. A reconciliation of the nonhorizontal plateau observed at finite compression rates with the first-order character of the LE/LC transition emerges then naturally from this kinetic scenario. New mechanical features are consequently assigned to the phase-separated monolayers made of stiff grains rafting in a fluid matrix. Particularly, for a raft-like lipid distribution, we hypothesize a finite rigidity kinetically controlled by the rate of domain growth and a high fluidity controlled by the continuous phase. We have depicted a minimal model of membrane mechanics that accounts for the elasticity of such a heterogeneous composite medium. This “Plum-cake” model is able to qualitatively predict the observed mechanical features and is suggested to describe raft-like membranes as compliant elastic media where lipid domains work as reservoirs able to exchange material with the surrounding fluid phase. Introduction Langmuir monolayers of fatty amphiphiles are known to undergo different structural transitions easily identifiable in the surface pressure isotherm measured at varying surface area (see classical reviews in refs 1–4). This method is primarily thermodynamic; therefore, it provides no direct information about the microscopic nature of the monolayer but only on the character of the surface phases and the transitions between them. Early workers recognized the existence of a complex monolayer polymorphism depending on the chemical structure and ther- modynamic variables mainly defined by lateral packing and temperature. 5,6 Specific surface microscopy techniques, fluo- rescence and Brewster angle methods for instance, have enabled a detailed description of the monolayer textures corresponding to the different monolayer phases appearing as a consequence of lateral packing. Molecular packing is usually varied as the surface area available to the monolayer is decreased under continuous lateral compression exerted by the barriers of the Langmuir trough. However, kinetic effects related to relatively high compression speeds give rise to metastable states which have been frequently invoked as a plausible source for unex- pected monolayer features, such as the subtle structural differ- ences between hypothetic different solid phases at high packing 6 or the nonhorizontal nature of the coexistence plateaux exhibited by a variety of lipid monolayers. 7 As far as a lipid bilayer consists of two weakly coupled monolayers, monolayers of phospholipids have been traditionally studied as models of biological membranes. 1,3,8 In analogy with the structural fluid-to-gel transition of bilayer membranes, the main transition of phospholipid monolayers is observed at a given pressure defining the coexistence plateau between the liquid-condensed disperse phase (LC ≡ gel) growing at the expense of the continuous liquid-expanded phase (LE ≡ fluid). The nature of this main LE/LC phase transition has been much discussed, being most frequently suggested to be of first order as an isothermal coexistence between two phases is observed in microscopy experiments. 1–4,8–10 However, nonhorizontal isotherm slopes are usually found in continuous compression experiments performed at a standard finite rate; thereby, the LE/ LC transition has been frequently claimed to be higher order. 1,9 On the finding that isotherm slopes are reduced under electro- static screening, alternative explanations have included long- range repulsive forces between polar heads as a possible source of plateau nonhorizontality. 11,12 However, any realistic estimate of electrostatic effects, even for charged phospholipids, yields a too low contribution to surface tension to ascribe the observed slopes to these forces. 1 * To whom correspondence should be addressed. † Universidad Complutense de Madrid. ‡ Universidad de Barcelona. J. Phys. Chem. B 2010, 114, 4509–4520 4509 10.1021/jp9118953  2010 American Chemical Society Published on Web 03/17/2010