“Certosino”

Dixon, James Henry

doi:10.1093/nq/s4-vii.158.19g

Cited by 7 publications

(7 citation statements)

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“…QCM-D enables realtime monitoring of binding kinetics and changes in thin film properties, and is therefore becoming increasingly popular for probing biological interfaces [81][82][83]. The model membrane platform was first assembled on the sensor chip before monitoring membrane association of the AH peptide.…”

Section: Engineering Strategy To Mimic Biological Membranesmentioning

confidence: 99%

Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

Jackman

Cho

2012

Biointerphases

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As one of the most important interfaces in cellular systems, biological membranes have essential functions in many activities such as cellular protection and signaling. Beyond their direct functions, they also serve as scaffolds to support the association of proteins involved in structural support, adhesion, and transport. Unfortunately, biological processes sometimes malfunction and require therapeutic intervention. For those processes which occur within or upon membranes, it is oftentimes difficult to study the mechanism in a biologically relevant, membranous environment. Therefore, the identification of direct therapeutic targets is challenging. In order to overcome this barrier, engineering strategies offer a new approach to interrogate biological activities at membrane interfaces by analyzing them through the principles of the interfacial sciences. Since membranes are complex biological interfaces, the development of simplified model systems which mimic important properties of membranes can enable fundamental characterization of interaction parameters for such processes. We have selected the hepatitis C virus (HCV) as a model viral pathogen to demonstrate how model membrane platforms can aid antiviral drug discovery and development. Responsible for generating the genomic diversity that makes treating HCV infection so difficult, viral replication represents an ideal step in the virus life cycle for therapeutic intervention. To target HCV genome replication, the interaction of viral proteins with model membrane platforms has served as a useful strategy for target identification and characterization. In this review article, we demonstrate how engineering approaches have led to the discovery of a new functional activity encoded within the HCV nonstructural 5A protein. Specifically, its N-terminal amphipathic, α-helix (AH) can rupture lipid vesicles in a size-dependent manner. While this activity has a number of exciting biotechnology and biomedical applications, arguably the most promising one is in antiviral medicine. Based on the similarities between lipid vesicles and the lipid envelopes of virus particles, experimental findings from model membrane platforms led to the prediction that a range of medically important viruses might be susceptible to rupturing treatment with synthetic AH peptide. This hypothesis was tested and validated by molecular virology studies. Broad-spectrum antiviral activity of the AH peptide has been identified against HCV, HIV, herpes simplex virus, and dengue virus, and many more deadly pathogens. As a result, the AH peptide is the first in class of broad-spectrum, lipid envelope-rupturing antiviral agents, and has entered the drug pipeline. In summary, engineering strategies break down complex biological systems into simplified biomimetic models that recapitulate the most important parameters. This approach is particularly advantageous for membrane-associated biological processes because model membrane platforms provide more direct characterization of target interactions than is possible with other methods. Consequently, model membrane platforms hold great promise for solving important biomedical problems and speeding up the translation of biological knowledge into clinical applications.

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Section: Engineering Strategy To Mimic Biological Membranesmentioning

confidence: 99%

Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

Jackman

Cho

2012

Biointerphases

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“…QCM-D is routinely used for the detection of nanogram quantities of bound analyte and is based on the principle that a decrease in the oscillation frequency (f) of a vibrating crystal is linearly correlated with mass loading (Rodahl et al, 1995;Dixon, 2008). QCM-D possesses a broad range of solution-surface measurement capabilities and has found practical application in the study of small molecule self-assembled monolayer formation (Nakano et al, 2003;Newman and Blanchard, 2007), analytical electrochemistry (Wang and Jiang, 2000;Marx and Zhou, 2002) and in the development of protein/nucleic acid biosensors (Feng et al, 2007;Peh et al, 2007;Yao et al, 2008).…”

Section: Qcm-d Modeling Of Ternary Complex Capturementioning

confidence: 99%

SERS detection of indirect viral DNA capture using colloidal gold and methylene blue as a Raman label

Harpster¹,

Zhang

Sankara-Warrier

et al. 2009

Biosensors and Bioelectronics

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“…[18][19][20][21] Detailed reviews offer an exhaustive overview on the topic. [22][23][24] The advantage of QCM-D is that both adsorbed amount and layer viscoelasticity can be monitored. The former is obtained from the shift of oscillation frequency (Df) of the substrate-coated quartz crystal, the latter from the energy dissipated by the system (DD) during the shear mode oscillation.…”

Section: Introductionmentioning

confidence: 99%

Short versus long chain polyelectrolyte multilayers: a direct comparison of self-assembly and structural properties

Micciulla

Dodoo

Chevigny

et al. 2014

Phys. Chem. Chem. Phys.

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a Successful layer-by-layer (LbL) growth of short chain (B30 repeat units per chain) poly(sodium styrene sulfonate) (PSS)-poly(diallyl dimethylammonium chloride) (PDADMAC) multilayers is presented for the first time and compared with the growth of equivalent long chain polyelectrolyte multilayers (PEMs). A detailed study performed by quartz crystal microbalance with dissipation (QCM-D) is carried out and three main processes are identified: (i) initial mass uptake, (ii) adsorption-desorption during layer equilibration and (iii) desorption during rinsing. In contrast to the high stability and strong layer increment of high molecular weight (HMW) PEMs, layer degradation characterizes low molecular weight (LMW) multilayers. In particular, two different instability phenomena are observed: a constant decrease of sensed mass during equilibration after PDADMAC adsorption, and a strong mass loss by salt-free rinsing after PSS adsorption. Yet, an increase of salt concentration leads to much stronger layer growth.First, when the rinsing medium is changed from pure water to 0.1 M NaCl, the mass loss during rinsing is reduced, irrespective of molecular weight. Second, an increase in salt concentration in the LMW PE solutions causes a larger increment during the initial adsorption step, with no effect on the rinsing.Finally, the mechanical properties of the two systems are extracted from the measured frequency and dissipation shifts, as they offer a deeper insight into the multilayer structures depending on chain length and outermost layer. The paper enriches the field of PE assembly by presenting the use of very short PE chains to form multilayers and elucidates the role of preparation conditions to overcome the limitation of layer stability.

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“Certosino”

Cited by 7 publications

References 0 publications

Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

SERS detection of indirect viral DNA capture using colloidal gold and methylene blue as a Raman label

Short versus long chain polyelectrolyte multilayers: a direct comparison of self-assembly and structural properties

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