Increased membrane fluidity implicated in acceleration of decay of post-tetanic potentiation by alcohols

Woodson, Paul B.J.; Traynor, M. Elaine; Schlapfer, Werner T.; Barondes, Samuel H.

doi:10.1038/260797a0

Cited by 39 publications

(5 citation statements)

References 8 publications

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“…Membrane fluidity is determined by the lipid composition of the membranes (Los and Murata, 2004), and substances which alter membrane fluidity also alter physiological function in cells (Woodson et al, 1976). Ortho-substituted PCBs are cytotoxic and alter [Ca 2+ ] i homeostasis in neurons (Kodavanti et al, 1993;Tan et al, 2004;Wong et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Effects of PCB 52 and PCB 77 on cell viability, [Ca2+]i levels and membrane fluidity in mouse thymocytes

et al. 2006

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Section: Introductionmentioning

confidence: 99%

Effects of PCB 52 and PCB 77 on cell viability, [Ca2+]i levels and membrane fluidity in mouse thymocytes

et al. 2006

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“…In lipid systems, the existence of such regions has been experimentally demonstrated by neutron scattering, − single-molecule tracking studies, , and rotational probe dynamics, as well as molecular simulation. − The partitioning of membranes into laterally heterogeneous domains having different mobilities creates a tunable environment to modulate protein interactions and other cellular functions. Accordingly, the dynamical heterogeneity could give rise to intermittency of protein displacements in membranes, , and membrane fluidity shows a strong sensitivity to molecular additives (e.g., anesthetics, antibiotics, neurotransmitters, proteins) that influence molecular packing. − While there is widespread acknowledgment of the importance of these transient structures, a precise and quantifiable definition of heterogeneous dynamics in membranes remains a challenge …”

Section: Introductionmentioning

confidence: 99%

Quantifying the Heterogeneous Dynamics of a Simulated Dipalmitoylphosphatidylcholine (DPPC) Membrane

Shafique¹,

Kennedy²,

Douglas

et al. 2016

J. Phys. Chem. B

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Heterogeneity of dynamics plays a vital role in membrane function, but the methods for quantifying this heterogeneity are still being developed. Here we examine membrane dynamical heterogeneity via molecular simulations of a single-component dipalmitoylphosphatidylcholine (DPPC) lipid bilayer using the MARTINI force field. We draw upon well-established analysis methods developed in the study of glass-forming fluids and find significant changes in lipid dynamics between the fluid (Lα), and gel (Lβ) phases. In particular, we distinguish two mobility groups in the more ordered Lβ phase: (i) lipids that are transiently trapped by their neighbors and (ii) lipids with displacements on the scale of the intermolecular spacing. These distinct mobility groups spatially segregate, forming dynamic clusters that have characteristic time (1-2 μs) and length (1-10 nm) scales comparable to those of proteins and other biomolecules. We suggest that these dynamic clusters could couple to biomolecules within the membrane and thus may play a role in many membrane functions. In the equilibrium membrane, lipid molecules dynamically exchange between the mobility groups, and the resulting clusters are not associated with a thermodynamic phase separation. Dynamical clusters having similar characteristics arise in many other condensed phase materials, placing membranes in a broad class of materials with strong intermolecular interactions.

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“…Any unifying framework for the dynamics of membranes and ra-like heterogeneity must account for a number of basic physical characteristics, including: (i) the occurrence of coexisting "immobile" and "mobile" lipid molecules that exhibit different displacement kinetics in single-particle molecular tracking studies; 5,14 (ii) intermittency of protein displacements, the occurrence of coexisting mobile and immobile protein populations, and the correlated displacement of proteins within cells; 15,16 (iii) the occurrence of collective particle rearrangement motions, a phenomenon observed directly in membrane associated proteins in living cells, 15,17 as well as in model lipid membranes; 6,7 (iv) the formation of island and hole structures of the membrane topography that seem to persist at equilibrium, even in single-component lipid lms; 4,18,19 (v) a strong sensitivity of the uidity of lipid membranes to molecular additives (e.g., anesthetics, antibiotics, neurotransmitters, proteins) that inuence molecular packing in the lipid layer. [20][21][22][23][24][25][26] Many of the referenced studies have emphasized the shortcomings of continuum theory for these materials, and some invoke free volume ideas developed in the theory of glassforming liquids to rationalize trends in lipid mobility data, [27][28][29] further suggesting the connection to the physics of glassforming liquids.…”

Section: Introductionmentioning

confidence: 99%

Dynamical clustering and a mechanism for raft-like structures in a model lipid membrane

2014

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We use molecular dynamics simulations to examine the dynamical heterogeneity of a model single-component lipid membrane using a coarse-grained representation of lipid molecules. This model qualitatively reproduces the known phase transitions between disordered, ordered, and gel membrane phases, and the phase transitions are accompanied by significant changes in the nature of the lipid dynamics. In particular, lipid diffusion in the liquid-ordered phase is hindered by the transient trapping of molecules by their neighbors, similar to the dynamics of a liquid approaching its glass transition. This transient molecular caging gives rise to two distinct mobility groups within a single-component membrane: lipids that are transiently trapped, and lipids with displacements on the scale of the intermolecular spacing. Most significantly, lipids within these distinct mobility states spatially segregate, creating transient “islands” of enhanced mobility having a size and time scale compatible with lipid “rafts,” dynamical structures thought to be important for cell membrane function. Although the dynamic lipid clusters that we observe do not themselves correspond to rafts (which are more complex, multicomponent structures), we hypothesize that such rafts may develop from the same universal mechanism, explaining why raft-like regions should arise, regardless of lipid structural or compositional details. These clusters are strikingly similar to the dynamical clusters found in glass-forming fluids, and distinct from phase-separation clusters. Further examination shows that mobile lipid clusters can be dissected into smaller clusters of cooperatively rearranging molecules. The geometry of these clusters can be understood in the context of branched equilibrium polymers, related to the statistics percolation theory. We discuss how these dynamical structures relate to a range observations on the dynamics of lipid membranes.

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Increased membrane fluidity implicated in acceleration of decay of post-tetanic potentiation by alcohols

Cited by 39 publications

References 8 publications

Effects of PCB 52 and PCB 77 on cell viability, [Ca2+]i levels and membrane fluidity in mouse thymocytes

Effects of PCB 52 and PCB 77 on cell viability, [Ca2+]i levels and membrane fluidity in mouse thymocytes

Quantifying the Heterogeneous Dynamics of a Simulated Dipalmitoylphosphatidylcholine (DPPC) Membrane

Dynamical clustering and a mechanism for raft-like structures in a model lipid membrane

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