Publications by year, excluding conference proceedings.
Complete CV Google Scholar Page
2019
Kennedy, Kiley E; Shafique, Neha; Douglas, Jack F; Starr, Francis W
Cooperative dynamics in a model DPPC membrane arise from membrane layer interactions Journal Article
In: Emergent Materials, vol. 2, no. 1, pp. 1-10, 2019.
Abstract | BibTeX | Tags: Biophysics, Dynamic Heterogeneity, Membranes | Links:
@article{ksds19,
title = {Cooperative dynamics in a model DPPC membrane arise from membrane layer interactions},
author = {Kiley E Kennedy and Neha Shafique and Jack F Douglas and Francis W Starr},
url = {http://fstarr.web.wesleyan.edu/publications/ksds19.pdf},
doi = {10.1007/s42247-018-0020-2},
year = {2019},
date = {2019-03-01},
journal = {Emergent Materials},
volume = {2},
number = {1},
pages = {1-10},
abstract = {The dynamics of model membranes can be highly heterogeneous, especially in more ordered dense phases. To better understand the origins of this heterogeneity, as well as the degree to which monolayer systems mimic the dynamical properties of bilayer membranes, we use molecular simulations to contrast the dynamical behavior of a single-component dipalmitoylphosphatidylcholine (DPPC) lipid monolayer with that of a DPPC bilayer. DPPC is prevalent in both biological monolayers and bilayers, and we utilize the widely studied MARTINI model to describe the molecular interactions. As expected, our simulations confirm that the lateral structure of the monolayer and bilayer is nearly indistinguishable in both low- and high-density phases. Dynamically, the monolayer and bilayer both exhibit a drop in mobility for dense phases, but we find that there are substantial differences in the amplitude of these changes, as well as the nature of molecular displacements for these systems. Specifically, the monolayer exhibits no apparent cooperativity of the dynamics, while the bilayer shows substantial spatial and temporal heterogeneity in the dynamics. Consequently, the dynamical heterogeneity and cooperativity observed in the bilayer membrane case arises in part due to interlayer interactions. We indeed find a substantial interdigitation of the membrane leaflets which appears to impede molecular rearrangement. On the other hand, the monolayer, like the bilayer, does exhibit complex non-Brownian molecular displacements at intermediate time scales. For the monolayer system, the single particle motion can be well characterized by fractional Brownian motion, rather than being a consequence of strong correlations in the molecular motion previously observed in bilayer membranes. The significant differences in the dynamics of dense monolayers and bilayers suggest that care must be taken when making inferences about membrane dynamics on the basis of monolayer studies.},
keywords = {Biophysics, Dynamic Heterogeneity, Membranes},
pubstate = {published},
tppubtype = {article}
}
The dynamics of model membranes can be highly heterogeneous, especially in more ordered dense phases. To better understand the origins of this heterogeneity, as well as the degree to which monolayer systems mimic the dynamical properties of bilayer membranes, we use molecular simulations to contrast the dynamical behavior of a single-component dipalmitoylphosphatidylcholine (DPPC) lipid monolayer with that of a DPPC bilayer. DPPC is prevalent in both biological monolayers and bilayers, and we utilize the widely studied MARTINI model to describe the molecular interactions. As expected, our simulations confirm that the lateral structure of the monolayer and bilayer is nearly indistinguishable in both low- and high-density phases. Dynamically, the monolayer and bilayer both exhibit a drop in mobility for dense phases, but we find that there are substantial differences in the amplitude of these changes, as well as the nature of molecular displacements for these systems. Specifically, the monolayer exhibits no apparent cooperativity of the dynamics, while the bilayer shows substantial spatial and temporal heterogeneity in the dynamics. Consequently, the dynamical heterogeneity and cooperativity observed in the bilayer membrane case arises in part due to interlayer interactions. We indeed find a substantial interdigitation of the membrane leaflets which appears to impede molecular rearrangement. On the other hand, the monolayer, like the bilayer, does exhibit complex non-Brownian molecular displacements at intermediate time scales. For the monolayer system, the single particle motion can be well characterized by fractional Brownian motion, rather than being a consequence of strong correlations in the molecular motion previously observed in bilayer membranes. The significant differences in the dynamics of dense monolayers and bilayers suggest that care must be taken when making inferences about membrane dynamics on the basis of monolayer studies.
2016
Shafique, Neha; Kennedy, Kiley E.; Douglas, Jack F.; Starr, Francis W.
Quantifying the Heterogeneous Dynamics of a Simulated DPPC Membrane Journal Article
In: JOURNAL OF PHYSICAL CHEMISTRY B, vol. 120, no. 23, pp. 5172–5182, 2016, (PMID: 27223339).
Abstract | BibTeX | Tags: Biophysics, Dynamic Heterogeneity, Membranes | Links:
@article{skds16,
title = {Quantifying the Heterogeneous Dynamics of a Simulated DPPC Membrane},
author = {Neha Shafique and Kiley E. Kennedy and Jack F. Douglas and Francis W. Starr},
url = {http://fstarr.web.wesleyan.edu/publications/skds16-links.pdf},
doi = {10.1021/acs.jpcb.6b02982},
year = {2016},
date = {2016-05-25},
journal = {JOURNAL OF PHYSICAL CHEMISTRY B},
volume = {120},
number = {23},
pages = {5172–5182},
abstract = {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.},
note = {PMID: 27223339},
keywords = {Biophysics, Dynamic Heterogeneity, Membranes},
pubstate = {published},
tppubtype = {article}
}
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.
2014
Starr, Francis W.; Hartmann, Benedikt; Douglas, Jack F.
Dynamical clustering and a mechanism for raft-like structures in a model lipid membrane Journal Article
In: SOFT MATTER, vol. 10, no. 17, pp. 3036-3047, 2014, ISSN: 1744-683X.
Abstract | BibTeX | Tags: Biophysics, Dynamic Heterogeneity, Membranes | Links:
@article{shd14,
title = {Dynamical clustering and a mechanism for raft-like structures in a model lipid membrane},
author = {Starr, Francis W. and Hartmann, Benedikt and Douglas, Jack F.},
url = {http://fstarr.web.wesleyan.edu/publications/shd14.pdf},
doi = {10.1039/c3sm53187b},
issn = {1744-683X},
year = {2014},
date = {2014-01-01},
journal = {SOFT MATTER},
volume = {10},
number = {17},
pages = {3036-3047},
abstract = {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. We also show 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 percolation theory. We discuss how these dynamical structures relate to a range observations on the dynamics of lipid membranes.},
keywords = {Biophysics, Dynamic Heterogeneity, Membranes},
pubstate = {published},
tppubtype = {article}
}
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. We also show 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 percolation theory. We discuss how these dynamical structures relate to a range observations on the dynamics of lipid membranes.