Probing Membrane Insertion Activity of Antimicrobial Polymers via Coarse-Grain Molecular Dynamics

López, Carlos F.; Nielsen, Steven O.; Srinivas, Goundla; DeGrado, William F.; Klein, Michael L.

doi:10.1021/ct050298p

Cited by 53 publications

(59 citation statements)

References 36 publications

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“…In late-stage attack, antimicrobials cross the membrane core and occasionally align to provide a steppingstone pathway for water permeation. This is consistent with the mechanism described earlier suggesting a possible new mode of action that does not depend on pore formation for transport to and across the inner leaflet [212].…”

Section: 214supporting

confidence: 92%

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Infectious disease: Connecting innate immunity to biocidal polymers

Gabriel

Som

Madkour

et al. 2007

Materials Science and Engineering: R: Reports

253

258

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Infectious disease is a critically important global healthcare issue. In the U.S. alone there are 2 million new cases of hospital-acquired infections annually leading to 90,000 deaths and 5 billion dollars of added healthcare costs. Couple these numbers with the appearance of new antibiotic resistant bacterial strains and the increasing occurrences of community-type outbreaks, and clearly this is an important problem. Our review attempts to bridge the research areas of natural host defense peptides (HDPs), a component of the innate immune system, and biocidal cationic polymers. Recently discovered peptidomimetics and other synthetic mimics of HDPs, that can be short oligomers as well as polymeric macromolecules, provide a unique link between these two areas. An emerging class of these mimics are the facially amphiphilic polymers that aim to emulate the physicochemical properties of HDPs but take advantage of the synthetic ease of polymers. These mimics have been designed with antimicrobial activity and, importantly, selectivity that rivals natural HDPs. In addition to providing some perspective on HDPs, selective mimics, and biocidal polymers, focus is given to the arsenal of biophysical techniques available to study their mode of action and interactions with phospholipid membranes. The issue of lipid type is highlighted and the important role of negative curvature lipids is illustrated. Finally, materials applications (for instance, in the development of permanently antibacterial surfaces) are discussed as this is an important part of controlling the spread of infectious disease.

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Section: 214supporting

confidence: 92%

“…[58,72,212] The system differed by composition (i.e. the ratio of hydrophobic to charge units), length (8, 10, or 20 monomer units) and sequence (alternating vs. block copolymers).…”

Section: 214mentioning

confidence: 99%

Infectious disease: Connecting innate immunity to biocidal polymers

Gabriel

Som

Madkour

et al. 2007

Materials Science and Engineering: R: Reports

253

258

View full text Add to dashboard Cite

show abstract

“…The studies of different bilayer phases [ 187,180,206,191,175], of the kinetics of phase transition [ 207,208], of self-assembly [ 171,438,439,411], and of phase separation in membrane consisting of different components [ 440,114,441,192,442,443,444,445,446,447,233] have already yielded important information about these fascinating systems. Other important questions that can be tackled by coarse-grained models include the interaction between membranes, between membranes and solid substrates, and the interplay between membrane collective phenomena and peptides, proteins and polymers [ 448,449,450,451,452,183,453], or active components (e.g., ion pumps [ 454,455,456,457,183], or fusion proteins [ 404,458]). …”

Section: Discussionmentioning

confidence: 99%

Biological and synthetic membranes: What can be learned from a coarse-grained description?

2006

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We discuss the role coarse-grained models play in the investigation of the structure and thermodynamics of bilayer membranes, and we place them in the context of alternative approaches. Because they reduce the degrees of freedom and employ simple and soft effective potentials, coarse-grained models can provide rather direct insight into collective phenomena in membranes on large time and length scales. We present a summary of recent progress in this rapidly evolving field, and pay special attention to model development and computational techniques. Applications of coarse-grained models to changes of the membrane topology are illustrated with studies of membrane fusion utilizing simulations and self-consistent field theory.

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“…Using the same mesoscopic modeling approach, Lopez et al [236] also studied the spontaneous insertion of antimicrobial polymers into a lipid bilayer. Antimicrobial peptides attack the cell membrane of bacteria, causing its rupture and consequently cell death.…”

Section: Protein Insertion Into Membranesmentioning

confidence: 99%

Mesoscopic models of biological membranes

Venturoli¹,

et al. 2006

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Phospholipids are the main components of biological membranes and dissolved in water these molecules self-assemble into closed structures, of which bilayers are the most relevant from a biological point of view. Lipid bilayers are often used, both in experimental and by theoretical investigations, as model systems to understand the fundamental properties of biomembranes. The properties of lipid bilayers can be studied at different time and length scales. For some properties it is sufficient to envision a membrane as an elastic sheet, while for others it is important to take into account the details of the individual atoms. In this review, we focus on an intermediate level, where groups of atoms are lumped into pseudo-particles to arrive at a coarse-grained, or mesoscopic, description of a bilayer, which is subsequently studied using molecular simulation.The aim of this review is to compare various strategies to coarse grain a biological membrane. The conclusion of this comparison is that there can be many valid different strategies, but that the results obtained by the various mesoscopic models are surprisingly consistent. A second objective of this review is to illustrate how mesoscopic models can be used to obtain a better understanding of experimental systems. The advantage of coarse-grained models is that these can be simulated very efficiently, so that phenomena involving large systems, or requiring a large number of simulations, can be studied in detail. This is illustrated with the study of the relation between the phase behavior of a membrane and the structure of the phospholipids, and the membrane structural changes due to molecules (such as alcohols, cholesterol and anesthetics) adsorbed to the membrane. We then discuss the effect of transmembrane peptides on the local structure of a membrane and the mechanism of vesicle fusion and fission.

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Probing Membrane Insertion Activity of Antimicrobial Polymers via Coarse-Grain Molecular Dynamics

Cited by 53 publications

References 36 publications

Infectious disease: Connecting innate immunity to biocidal polymers

Infectious disease: Connecting innate immunity to biocidal polymers

Biological and synthetic membranes: What can be learned from a coarse-grained description?

Mesoscopic models of biological membranes

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