Cargando…

Carbohydrate-Derived Amphiphilic Macromolecules: A Biophysical Structural Characterization and Analysis of Binding Behaviors to Model Membranes

The design and synthesis of enhanced membrane-intercalating biomaterials for drug delivery or vascular membrane targeting is currently challenged by the lack of screening and prediction tools. The present work demonstrates the generation of a Quantitative Structural Activity Relationship model (QSAR...

Descripción completa

Detalles Bibliográficos
Autores principales: Martin, Adriana A. T., Tomasini, Michael, Kholodovych, Vladyslav, Gu, Li, Sommerfeld, Sven Daniel, Uhrich, Kathryn E., Murthy, N. Sanjeeva, Welsh, William J., Moghe, Prabhas V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493506/
https://www.ncbi.nlm.nih.gov/pubmed/25855953
http://dx.doi.org/10.3390/jfb6020171
_version_ 1782379929714819072
author Martin, Adriana A. T.
Tomasini, Michael
Kholodovych, Vladyslav
Gu, Li
Sommerfeld, Sven Daniel
Uhrich, Kathryn E.
Murthy, N. Sanjeeva
Welsh, William J.
Moghe, Prabhas V.
author_facet Martin, Adriana A. T.
Tomasini, Michael
Kholodovych, Vladyslav
Gu, Li
Sommerfeld, Sven Daniel
Uhrich, Kathryn E.
Murthy, N. Sanjeeva
Welsh, William J.
Moghe, Prabhas V.
author_sort Martin, Adriana A. T.
collection PubMed
description The design and synthesis of enhanced membrane-intercalating biomaterials for drug delivery or vascular membrane targeting is currently challenged by the lack of screening and prediction tools. The present work demonstrates the generation of a Quantitative Structural Activity Relationship model (QSAR) to make a priori predictions. Amphiphilic macromolecules (AMs) “stealth lipids” built on aldaric and uronic acids frameworks attached to poly(ethylene glycol) (PEG) polymer tails were developed to form self-assembling micelles. In the present study, a defined set of novel AM structures were investigated in terms of their binding to lipid membrane bilayers using Quartz Crystal Microbalance with Dissipation (QCM-D) experiments coupled with computational coarse-grained molecular dynamics (CG MD) and all-atom MD (AA MD) simulations. The CG MD simulations capture the insertion dynamics of the AM lipophilic backbones into the lipid bilayer with the PEGylated tail directed into bulk water. QCM-D measurements with Voigt viscoelastic model analysis enabled the quantitation of the mass gain and rate of interaction between the AM and the lipid bilayer surface. Thus, this study yielded insights about variations in the functional activity of AM materials with minute compositional or stereochemical differences based on membrane binding, which has translational potential for transplanting these materials in vivo. More broadly, it demonstrates an integrated computational-experimental approach, which can offer a promising strategy for the in silico design and screening of therapeutic candidate materials.
format Online
Article
Text
id pubmed-4493506
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-44935062015-07-07 Carbohydrate-Derived Amphiphilic Macromolecules: A Biophysical Structural Characterization and Analysis of Binding Behaviors to Model Membranes Martin, Adriana A. T. Tomasini, Michael Kholodovych, Vladyslav Gu, Li Sommerfeld, Sven Daniel Uhrich, Kathryn E. Murthy, N. Sanjeeva Welsh, William J. Moghe, Prabhas V. J Funct Biomater Article The design and synthesis of enhanced membrane-intercalating biomaterials for drug delivery or vascular membrane targeting is currently challenged by the lack of screening and prediction tools. The present work demonstrates the generation of a Quantitative Structural Activity Relationship model (QSAR) to make a priori predictions. Amphiphilic macromolecules (AMs) “stealth lipids” built on aldaric and uronic acids frameworks attached to poly(ethylene glycol) (PEG) polymer tails were developed to form self-assembling micelles. In the present study, a defined set of novel AM structures were investigated in terms of their binding to lipid membrane bilayers using Quartz Crystal Microbalance with Dissipation (QCM-D) experiments coupled with computational coarse-grained molecular dynamics (CG MD) and all-atom MD (AA MD) simulations. The CG MD simulations capture the insertion dynamics of the AM lipophilic backbones into the lipid bilayer with the PEGylated tail directed into bulk water. QCM-D measurements with Voigt viscoelastic model analysis enabled the quantitation of the mass gain and rate of interaction between the AM and the lipid bilayer surface. Thus, this study yielded insights about variations in the functional activity of AM materials with minute compositional or stereochemical differences based on membrane binding, which has translational potential for transplanting these materials in vivo. More broadly, it demonstrates an integrated computational-experimental approach, which can offer a promising strategy for the in silico design and screening of therapeutic candidate materials. MDPI 2015-04-08 /pmc/articles/PMC4493506/ /pubmed/25855953 http://dx.doi.org/10.3390/jfb6020171 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Martin, Adriana A. T.
Tomasini, Michael
Kholodovych, Vladyslav
Gu, Li
Sommerfeld, Sven Daniel
Uhrich, Kathryn E.
Murthy, N. Sanjeeva
Welsh, William J.
Moghe, Prabhas V.
Carbohydrate-Derived Amphiphilic Macromolecules: A Biophysical Structural Characterization and Analysis of Binding Behaviors to Model Membranes
title Carbohydrate-Derived Amphiphilic Macromolecules: A Biophysical Structural Characterization and Analysis of Binding Behaviors to Model Membranes
title_full Carbohydrate-Derived Amphiphilic Macromolecules: A Biophysical Structural Characterization and Analysis of Binding Behaviors to Model Membranes
title_fullStr Carbohydrate-Derived Amphiphilic Macromolecules: A Biophysical Structural Characterization and Analysis of Binding Behaviors to Model Membranes
title_full_unstemmed Carbohydrate-Derived Amphiphilic Macromolecules: A Biophysical Structural Characterization and Analysis of Binding Behaviors to Model Membranes
title_short Carbohydrate-Derived Amphiphilic Macromolecules: A Biophysical Structural Characterization and Analysis of Binding Behaviors to Model Membranes
title_sort carbohydrate-derived amphiphilic macromolecules: a biophysical structural characterization and analysis of binding behaviors to model membranes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493506/
https://www.ncbi.nlm.nih.gov/pubmed/25855953
http://dx.doi.org/10.3390/jfb6020171
work_keys_str_mv AT martinadrianaat carbohydratederivedamphiphilicmacromoleculesabiophysicalstructuralcharacterizationandanalysisofbindingbehaviorstomodelmembranes
AT tomasinimichael carbohydratederivedamphiphilicmacromoleculesabiophysicalstructuralcharacterizationandanalysisofbindingbehaviorstomodelmembranes
AT kholodovychvladyslav carbohydratederivedamphiphilicmacromoleculesabiophysicalstructuralcharacterizationandanalysisofbindingbehaviorstomodelmembranes
AT guli carbohydratederivedamphiphilicmacromoleculesabiophysicalstructuralcharacterizationandanalysisofbindingbehaviorstomodelmembranes
AT sommerfeldsvendaniel carbohydratederivedamphiphilicmacromoleculesabiophysicalstructuralcharacterizationandanalysisofbindingbehaviorstomodelmembranes
AT uhrichkathryne carbohydratederivedamphiphilicmacromoleculesabiophysicalstructuralcharacterizationandanalysisofbindingbehaviorstomodelmembranes
AT murthynsanjeeva carbohydratederivedamphiphilicmacromoleculesabiophysicalstructuralcharacterizationandanalysisofbindingbehaviorstomodelmembranes
AT welshwilliamj carbohydratederivedamphiphilicmacromoleculesabiophysicalstructuralcharacterizationandanalysisofbindingbehaviorstomodelmembranes
AT mogheprabhasv carbohydratederivedamphiphilicmacromoleculesabiophysicalstructuralcharacterizationandanalysisofbindingbehaviorstomodelmembranes