Cholesterol Conjugated Elastin-like Recombinamers: Molecular Dynamics Simulations, Conformational Changes, and Bioactivity
Year: 2024
Type: article
Abstract: Current models for elastin-like recombinamer (ELR) design struggle to predict the effects of nonprotein fused materials on polypeptide conformation and temperature-responsive properties. To address this shortage, we investigated the novel functionalization of ELRs with cholesterol (CTA). We employed GROMACS computational molecular dynamic simulations complemented with experimental evidence to validate the in silico predictions. The ELR CTA was biosynthesized and characterized by using fluorescence assays, circular dichroism, dynamic light scattering, and differential scanning calorimetry. The in silico and in vitro data showed that CTA promotes the formation of intramolecular hydrogen bonds that favor β-sheet secondary structures. Compared with an unmodified ELR VKV, CTA enhanced the hydrophobicity and stability of the system, allowing the formation of monodisperse nanoaggregates at physiologically relevant temperatures. Importantly, calorimetry assays revealed that ELR CTA interacted and intercalated with the lipid bilayers of the DPPC liposomes. To demonstrate the implications of these changes for biomedical applications, ELR CTA and DPPC-ELR CTA hybrid nanoparticles were tested with cancer and immune cell lines. Interactions with the cell membranes demonstrated a synergistic effect of the composition and size of the modified recombinamer aggregates on the internalization. The results indicated the potential use of ELR-based nanoparticles for localized and systemic drug delivery. This work sets a new precedent to design elastin-inspired biomaterials with predictable self-assembly properties and develop novel drug delivery strategies.
Institutions: Universidade de Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago, 3B's Research Group, University of Minho, Consejo Superior de Investigaciones Científicas, Bielefeld University, Instituto de Investigacións Mariñas, Universidad de Valladolid, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: green
Awards: G1496055848, Microcápsulas Poliméricas Obtidas por Automontagem Camada-a-Camada em Suportes Inorgânicos Com Capacidade de Encapsulamento Multimodal de Drogas Para o Tratamento do Cancro da Mama, SmartShuttle – Tackling Tumor Heterogeneity Using Biomaterial-Based Multifunctional Nanocarriers Against Cancer, G4820502543, G5587996612, PolyTarget - Polyelectrolyte-Based Nanocarriers with Prospects of Targeting Breast Cancer Multiresistances
OpenAlex ID: W4404520352