Grafting density and colocation affect cell internalisation of peptide decorated nanoparticles: when less is more! — ASN Events
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  3. Grafting density and colocation affect cell internalisation of peptide decorated nanoparticles: when less is more!

Grafting density and colocation affect cell internalisation of peptide decorated nanoparticles: when less is more! (#13)

Nevena Todorova 1 , Ciro Chiappini 2 , Morgan Mager 2 , Benjamin Simona 2 , Molly M Stevens 2 , Irene Yarovsky
  1. SAMME and Health Innovations Research Institute, RMIT University, Melbourne, VIC, Australia
  2. Department of Materials, Department of Bioengineering and Institute for Biomedical Engineering, Imperial College London, London, UK

Nanoparticle functionalisation with peptides has proven to be a good strategy to inhibit particle aggregation, increase nanoparticle solubility and develop potential nanocarriers.1  Cell-penetrating peptides, such as, for example, the transcription transactivation TAT peptide from human HIV-1 virus, have become a popular choice for transfection and other types of cellular delivery.2  Remarkably, studies have shown that TAT-peptide functionalized gold nanoparticles have the ability to penetrate cell membranes and localise in the nucleus.3,4 

Detailed investigation of the peptide concentration and distribution in the functional-peptide layer at all-atom resolution is crucial for an improved understanding of specific nanoparticle interactions with biological systems which will aid the design of nanomaterials for targeted applications. With this in mind, we have performed an experimental and computational study on the effects of TAT peptide concentration on the structure and dynamics of the peptide layer on the 3 nm AuNP surface and its impact on the NP's membrane permeation capacity.

We show that cell internalisation of TAT functionalised nanoparticles is strongly dependent on TAT surface concentration and distribution. We present the mechanism by which TAT may become inactive upon surface immobilisation and demonstrate how the local environment of the functional peptide grafted onto the nanoparticle surface may affect properties essential for efficient cellular uptake. We found that a notably increased membrane activity correlates with the peptide backbone rigidity and increased basic residue solvent exposure attained at a particular concentration range of the functional peptides. The theoretically predicted membrane permeating capacity was confirmed experimentally while we also revealed molecular properties relevant to the experimentally observed inactivation with increasing TAT concentration. Our results suggest that nanoparticles may be engineered to specifically permeate membranes by targeted conjugation of peptides at specific concentrations and spacing.

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  1. A. Makarucha, N. Todorova, I. Yarovsky “Nanomaterials in biological environment: a review of computer modelling studies” European Biophysical Journal, 40(2):103 (2011)
  2. N.A. Brooks, et al. “Cell- penetrating peptides: Application in vaccine delivery”, Biochemica et Biophysica Acta, 1805:25 (2010)
  3. Krpetic, Z. et al. “Negotiation of intracellular membrane barriers by TAT-modified gold nanoparticles.” ACS Nano 5:5201 (2011)
  4. J.M de la Fuente and C.C. Berry “Tat peptide as an efficient molecule to translocate gold nanoparticles into the cell nucleus”, Bioconjugate Chem. 16:1176 (2005)