Journal article
Membrane-Disrupting Nanofibrous Peptide Hydrogels
ACS biomaterials science & engineering, Vol.5(9), pp.4657-4670
09 Sep 2019
PMID: 33448838
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Self-assembled peptide nanofibers can form biomimetic hydrogels at physiological pH and ionic strength through noncovalent and reversible interactions. Inspired by natural antimicrobial peptides, we designed a class of cationic amphiphilic self-assembled peptides (CASPs) that self-assemble into thixotropic nanofibrous hydrogels. These constructs employ amphiphilicity and high terminal charge density to disrupt bacterial membranes. Here, we focus on three aspects of the self-assembly of these hydrogels: (a) the material properties of the individual self-assembled nanofibers, (b) emergence of bulk-scale elasticity in the nanofibrous hydrogel, and (c) trade-off between the desirable material properties and antimicrobial efficacy. The design of the supramolecular nanofibers allows for higher-order noncovalent ionic cross-linking of the nanofibers into a viscoelastic network. We determine the stiffness of the self-assembled nanofibers via the peak force quantitative nanomechanical atomic force microscopy and the bulk-scale rheometry. The storage moduli depend on peptide concentration, ionic strength, and concentration of multivalent ionic cross- linker. CASP nanofibers are demonstrated to be effective against Pseudomonas aeruginosa colonies. We use nanomechanical analysis and microsecond-time scale coarse-grained simulation to elucidate the interaction between the peptides and bacterial membranes. We demonstrate that the membranes stiffen, contract, and buckle after binding to peptide nanofibers, allowing disruption of osmotic equilibrium between the intracellular and extracellular matrix. This is further associated with dramatic changes in cell morphology. Our studies suggest that self-assembled peptide nanofibrils can potentially acts as membrane-disrupting antimicrobial agents, which can be formulated as injectable hydrogels with tunable material properties.
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Details
- Title
- Membrane-Disrupting Nanofibrous Peptide Hydrogels
- Creators
- Biplab Sarkar - New Jersey Institute of TechnologyZain Siddiqui - New Jersey Institute of TechnologyPeter K. Nguyen - New Jersey Institute of TechnologyNamita Dube - TIFR Centre for Interdisciplinary SciencesWanyi Fu - New Jersey Institute of TechnologySteven Park - Rutgers, The State University of New JerseyShivani Jaisinghani - New Jersey Institute of TechnologyReshma Paul - New Jersey Institute of TechnologyStephen D. Kozuch - Seton Hall UniversityDaiyong Deng - New Jersey Institute of TechnologyPatricia Iglesias-Montoro - New Jersey Institute of TechnologyMengyan Li - New Jersey Institute of TechnologyDavid Sabatino - Seton Hall UniversityDavid S. Perlin - Rutgers, The State University of New JerseyWen Zhang - New Jersey Institute of TechnologyJagannath Mondal - TIFR Centre for Interdisciplinary SciencesVivek A. Kumar - New Jersey Institute of Technology
- Publication Details
- ACS biomaterials science & engineering, Vol.5(9), pp.4657-4670
- Publisher
- Amer Chemical Soc
- Number of pages
- 27
- Grant note
- NJIT
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Identifiers
- 991021956861204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Materials Science, Biomaterials