Minimum Energy Path to Membrane Pore Formation and Rupture

Ting, Christina; Appelö, Daniel; Wang, Zhen‐Gang

doi:10.1103/physrevlett.106.168101

Cited by 68 publications

(74 citation statements)

References 31 publications

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“…They also found that higher generations of the dendrimer provided more stable pore structure in the membrane; this result is consistent with that using coarse-grained simulation based on the MARTINI model [99]. Recently, Ting et al proposed more sophisticated model using SCFT combined with the string method [100] to calculate the minimum energy path to membrane pore formation and rupture [98]. The string method automatically determines the reaction coordinate of the minimum energy path and thus, provides a means by which one may consider the actual nucleation events for the pore formation induced by the dendrimer.…”

Section: Statistical Field Theoriessupporting

confidence: 62%

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Multiscale Modeling for Host-Guest Chemistry of Dendrimers in Solution

Kim

Lamm

2012

Polymers

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Dendrimers have been widely used as nanostructured carriers for guest species in a variety of applications in medicine, catalysis, and environmental remediation. Theory and simulation methods are an important complement to experimental approaches that are designed to develop a fundamental understanding about how dendrimers interact with guest molecules. This review focuses on computational studies aimed at providing a better understanding of the relevant physicochemical parameters at play in the binding and release mechanisms between polyamidoamine (PAMAM) dendrimers and guest species. We highlight recent contributions that model supramolecular dendrimer-guest complexes over the temporal and spatial scales spanned by simulation methods ranging from all-atom molecular dynamics to statistical field theory. The role of solvent effects on dendrimer-guest interactions and the importance of relating model parameters across multiple scales is discussed.

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Section: Statistical Field Theoriessupporting

confidence: 62%

“…In particular, SCFT has been widely used for the prediction of equilibrium mesophases in polymeric systems [94][95][96][97][98]. Field-based simulation approaches readily provide the decomposition of free energy into entropic and enthalpic contributions.…”

Section: Statistical Field Theoriesmentioning

confidence: 99%

Multiscale Modeling for Host-Guest Chemistry of Dendrimers in Solution

Kim

Lamm

2012

Polymers

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“…Importantly, the model has been shown to provide a representation of copolymer thin films that is in good agreement with available experimental data (19,20). We rely on the string method to identify the MFEP between two metastable states on a free energy landscape (21)(22)(23)(24)(25)(26)(27)). An initial string is constructed by linear interpolation between the two end states.…”

Section: Model and Methodsmentioning

confidence: 64%

Molecular pathways for defect annihilation in directed self-assembly

Hur

Thapar

Ramírez-Hernández

et al. 2015

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

140

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Over the last few years, the directed self-assembly of block copolymers by surface patterns has transitioned from academic curiosity to viable contender for commercial fabrication of nextgeneration nanocircuits by lithography. Recently, it has become apparent that kinetics, and not only thermodynamics, plays a key role for the ability of a polymeric material to self-assemble into a perfect, defect-free ordered state. Perfection, in this context, implies not more than one defect, with characteristic dimensions on the order of 5 nm, over a sample area as large as 100 cm 2 . In this work, we identify the key pathways and the corresponding free energy barriers for eliminating defects, and we demonstrate that an extraordinarily large thermodynamic driving force is not necessarily sufficient for their removal. By adopting a concerted computational and experimental approach, we explain the molecular origins of these barriers and how they depend on material characteristics, and we propose strategies designed to overcome them. The validity of our conclusions for industrially relevant patterning processes is established by relying on instruments and assembly lines that are only available at state-of-the-art fabrication facilities, and, through this confluence of fundamental and applied research, we are able to discern the evolution of morphology at the smallest relevant length scales-a handful of nanometers-and present a view of defect annihilation in directed self-assembly at an unprecedented level of detail.directed self-assembly | copolymer | defect | minimum free energy path | string method O ver the last decade, the directed self-assembly (DSA) of block copolymers has rapidly evolved from mere intellectual curiosity (1-4) to a potentially crucial step in the commercial fabrication of next-generation electronic circuits. Indeed, the characteristic length scale of ordered self-assembled copolymer domains is in the range of 5-50 nm. Furthermore, their size and shape can be manipulated through simple processing steps, thereby making them attractive for the production of semiconductor devices, nanofluidic devices, or high-density storage media (5, 6). The general idea behind copolymer DSA is that a surface patternchemical or topographic-can be used to guide the assembly of a polymeric material into an ordered, device-like structure that is free of defects. In so-called "density multiplication" patterning strategies (7,8), the spacing or pitch of the surface features can be much larger than the characteristic dimensions of the copolymer of interest. One can thus prepare coarse surface patterns, which are easier to create, and rely on the copolymer to self-assemble into features whose density is considerably larger. Fig. 1 shows a schematic representation of the process for obtaining a lamellar morphology on a stripe-patterned substrate under a one-to-three (or 3X) density multiplication strategy. Patterned stripes interact preferentially with one of the blocks and guide the assembly of thin copolymer films into ordered lam...

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“…Eventually the membrane ruptures, thus releasing the trapped nanoparticles into the cytosol. Importantly, membrane rupture is a thermally nucleated process [8][9][10][11][12][13] under the small to moderate tensions generated in the proton sponge hypothesis. 7,14 It is therefore possible to imagine that the nanoparticle takes a more direct role in the endosomal escape by interacting directly with the membrane to lower the nucleation barrier for rupture.…”

mentioning

confidence: 99%

“…Recently, two groups 13,25 have developed a powerful meanfield technique for studying minimum free energy paths (MFEPs) in self-assembled polymeric systems. The technique combines the self-consistent field theory (SCFT) 26 with the string method, 27,28 and overcomes the aforemetioned time scale and dimensionality challenges.…”

mentioning

confidence: 99%

Minimum free energy paths for a nanoparticle crossing the lipid membrane

Ting

Wang

2012

Soft Matter

Self Cite

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Within self-consistent field theory, we develop an ''on-the-fly'' string method to compute the minimum free energy path for several activated processes involving a charged, solvophobic nanoparticle and a lipid membrane. Under tensions well below the mechanical stability limit of the membrane, and in the regime where the event can occur on experimentally relevant time scales, our study suggests that there can be at least three competing pathways for crossing the membrane: (1) particle-assisted membrane rupture, (2) particle insertion into a metastable pore followed by translocation and membrane resealing, and (3) particle insertion into a metastable pore followed by membrane rupture. In the context of polymer-based gene delivery systems, we discuss the implications of these results for the endosomal escape mechanism.The interaction of nanoparticles with lipid membranes is a common theme underlying a number of important topics in bionanotechnology, ranging from cytotoxicity 1 to the delivery of therapeutics.2 In polymer-based gene delivery systems, 3 the nanoparticle is comprised of genetic material condensed with cationic polymers. Once internalized by the cell via endocytosis, the nanoparticles are enclosed within membrane-bound vesicles called endosomes, and are trafficked along the endolysosomal pathway, where acidification activates hydrolytic enzymes. 4Hence, the nanoparticle must escape the endosome before crossing the nuclear envelope for successful gene expression. Clearly, membrane-particle interactions play a central role in several key steps along the gene delivery pathway. In particular, understanding the endosomal escape mechanism provides a direct motivation for this study.In the proton-sponge hypothesis, 5-7 the nanoparticle plays an indirect role in its own endosomal escape by serving as a buffering substrate for protons. As additional protons are pumped into the endosome with an attendant influx of counterions, the increase in osmotic pressure translates to increased tension on the endosomal membrane. Eventually the membrane ruptures, thus releasing the trapped nanoparticles into the cytosol. Importantly, membrane rupture is a thermally nucleated process 8-13 under the small to moderate tensions generated in the proton sponge hypothesis.7,14 It is therefore possible to imagine that the nanoparticle takes a more direct role in the endosomal escape by interacting directly with the membrane to lower the nucleation barrier for rupture. We examine this scenario in the broader context of activated pathways involving membraneparticle interactions.A number of computational studies on membrane-particle systems have been conducted to elucidate the equilibrium structures, [15][16][17][18][19] as well as the dynamics under (nearly) spontaneous conditions 20,21 or when induced by an external force. 22 However, these studies have not addressed the thermally activated processes we are interested in here. Besides the long time scales associated with these rare events, a significant challenge arises because of th...

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Minimum Energy Path to Membrane Pore Formation and Rupture

Cited by 68 publications

References 31 publications

Multiscale Modeling for Host-Guest Chemistry of Dendrimers in Solution

Multiscale Modeling for Host-Guest Chemistry of Dendrimers in Solution

Molecular pathways for defect annihilation in directed self-assembly

Minimum free energy paths for a nanoparticle crossing the lipid membrane

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