Free energy of a trans-membrane pore calculated from atomistic molecular dynamics simulations

Wohlert, Jakob; Otter, Wouter K. den; Edholm, Olle; Briels, Willem J.

doi:10.1063/1.2171965

Cited by 151 publications

(226 citation statements)

References 49 publications

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“…The line tensions at the perimeter of the bilayer fold, p , were calculated from simulation of a semiperiodic bilayer slab in water. The obtained values are in agreement with previous simulations (50 pN) (33) and somewhat larger than experimental values (5-30 pN) (34,35). The line tension at the bilayer connection to the monolayer, c, was obtained from simulations of monolayers connected by a bilayer.…”

Section: Structure Of Lipid Aggregates Formed Upon Monolayer Collapsesupporting

confidence: 81%

The molecular mechanism of lipid monolayer collapse

Baoukina

Monticelli

Risselada

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

255

253

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Lipid monolayers at an air-water interface can be compressed laterally and reach high surface density. Beyond a certain threshold, they become unstable and collapse. Lipid monolayer collapse plays an important role in the regulation of surface tension at the air-liquid interface in the lungs. Although the structures of lipid aggregates formed upon collapse can be characterized experimentally, the mechanism leading to these structures is not fully understood. We investigate the molecular mechanism of monolayer collapse using molecular dynamics simulations. Upon lateral compression, the collapse begins with buckling of the monolayer, followed by folding of the buckle into a bilayer in the water phase. Folding leads to an increase in the monolayer surface tension, which reaches the equilibrium spreading value. Immediately after their formation, the bilayer folds have a flat semielliptical shape, in agreement with theoretical predictions. The folds undergo further transformation and form either flat circular bilayers or vesicles. The transformation pathway depends on macroscopic parameters of the system: the bending modulus, the line tension at the monolayer-bilayer connection, and the line tension at the bilayer perimeter. These parameters are determined by the system composition and temperature. Coexistence of the monolayer with lipid aggregates is favorable at lower tensions of the monolayerbilayer connection. Transformation into a vesicle reduces the energy of the fold perimeter and is facilitated for softer bilayers, e.g., those with a higher content of unsaturated lipids, or at higher temperatures.lung surfactant ͉ bilayer reservoir ͉ course grain ͉ vesicle budding ͉ molecular dynamics L ipid molecules are insoluble in both polar and apolar media because of their amphipathic nature. At polar-apolar interfaces, they form monomolecular films that reduce the surface tension. Lipid monolayers form the main structural component (Ϸ97% by weight) of lung surfactant at the gas-exchange interface in the lung alveoli (1) and constitute the outer layer of tear film in the eyes (2). The properties of lipid monolayers vary with their surface density (3). For example, the higher the density, the lower is the resulting surface tension at the interface. At a certain very high surface density, however, a further reduction of the surface tension is not possible: the monolayers become unstable at the interface and collapse (4) (see scheme in Fig. 1). Besides being of fundamental interest for surface science, lipid monolayer collapse is crucial for maintaining low surface tension at the gas-exchange interface in the lungs during breathing (5).Collapse is characterized by loss of material from the interface and can proceed through different pathways. The modes of collapse and the surface tension at which collapse occurs depend on the molecular composition of the monolayer and on temperature (6-13), which determine the morphology and material properties of the monolayer. Although lipid monolayers in the liquid state do not usually ...

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Section: Structure Of Lipid Aggregates Formed Upon Monolayer Collapsesupporting

confidence: 81%

The molecular mechanism of lipid monolayer collapse

Baoukina

Monticelli

Risselada

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

255

253

View full text Add to dashboard Cite

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“…3 Briels and colleagues determined the free energy profile for a pore in a dipalmitoylphosphatidylcholine membrane using atomistic molecular dynamics simulations and reported that no energy barrier exists between intact state O and state I, which supports model B. 13,14 Recently, Evans and Smith reported that the energy profile for a lipid membrane containing a pre-pore depends on the types of lipids composing the membrane. 4 The results of the present study clearly indicate that a free energy which does not depend on tension, U 0 , contributes significantly to U a based on the experimental results (not based on interpretation).…”

Section: Discussionmentioning

confidence: 99%

“…3(a-3)). [12][13][14][15] When the radius is small, the pre-pore is hydrophobic, but as the radius expands and reaches a critical value, the prepore becomes hydrophilic. [12][13][14][15] Atomistic molecular dynamics simulation results 13,14 indicate the structure of a hydrophilic pre-pore shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

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Communication: Activation energy of tension-induced pore formation in lipid membranes

Karal

Yamazaki

2015

The Journal of Chemical Physics

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Tension plays a vital role in pore formation in biomembranes, but the mechanism of pore formation remains unclear. We investigated the temperature dependence of the rate constant of constant tension (σ)-induced pore formation in giant unilamellar vesicles of lipid membranes using an experimental method we developed. By analyzing this result, we determined the activation energy (U a ) of tensioninduced pore formation as a function of tension. A constant (U 0 ) that does not depend on tension was found to contribute significantly to U a . Analysis of the activation energy clearly indicated that the dependence of U a on σ in the classical theory is correct, but that the classical theory of pore formation is not entirely correct due to the presence of U 0 . We can reasonably consider that U 0 is a nucleation free energy to form a hydrophilic pre-pore from a hydrophobic pre-pore or a region with lower lateral lipid density. After obtaining U 0 , the evolution of a pre-pore follows a classical theory. Our data provide valuable information that help explain the mechanism of tension-induced pore formation in biomembranes and lipid membranes. C 2015 AIP Publishing LLC. [http://dx

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“…With the recent advance of computational approaches, researchers have investigated pore formation on membranes using Monte Carlo simulations and molecular dynamics (MD) simulations, which can reveal the molecular process of pore formation (26)(27)(28)(29)(30). In a number of MD simulation studies, the TMP was conveniently modeled by an external electric field across the membranes without any involvement of ions (26,27).…”

Section: Introductionmentioning

confidence: 99%

Probing Lipid Bilayers under Ionic Imbalance

Lin

Alexander‐Katz

2016

Biophysical Journal

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Biological membranes are normally under a resting transmembrane potential (TMP), which originates from the ionic imbalance between extracellular fluids and cytosols, and serves as electric power storage for cells. In cell electroporation, the ionic imbalance builds up a high TMP, resulting in the poration of cell membranes. However, the relationship between ionic imbalance and TMP is not clearly understood, and little is known about the effect of ionic imbalance on the structure and dynamics of biological membranes. In this study, we used coarse-grained molecular dynamics to characterize a dipalmitoylphosphatidylcholine bilayer system under ionic imbalances ranging from 0 to~0.06 e charges per lipid (e/Lip). We found that the TMP displayed three distinct regimes: 1) a linear regime between 0 and 0.045 e/Lip, where the TMP increased linearly with ionic imbalance; 2) a yielding regime between~0.045 and 0.060 e/Lip, where the TMP displayed a plateau; and 3) a poration regime above~0.060 e/Lip, where we observed pore formation within the sampling time (80 ns). We found no structural changes in the linear regime, apart from a nonlinear increase in the area per lipid, whereas in the yielding regime the bilayer exhibited substantial thinning, leading to an excess of water and Na þ within the bilayer, as well as significant misalignment of the lipid tails. In the poration regime, lipid molecules diffused slightly faster. We also found that the fluid-to-gel phase transition temperature of the bilayer dropped below the normal value with increased ionic imbalances. Our results show that a high ionic imbalance can substantially alter the essential properties of the bilayer, making the bilayer more fluid like, or conversely, depolarization of a cell could in principle lead to membrane stiffening.

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Free energy of a trans-membrane pore calculated from atomistic molecular dynamics simulations

Cited by 151 publications

References 49 publications

The molecular mechanism of lipid monolayer collapse

The molecular mechanism of lipid monolayer collapse

Communication: Activation energy of tension-induced pore formation in lipid membranes

Probing Lipid Bilayers under Ionic Imbalance

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