@article{Espinoza-Arcos2026,

title = {Lipid Composition Determines Hybrid Nanoparticle Selectivity: Beyond Membrane Mimicry in Cancer Targeting},

author = {L. Gonzalo Espinoza-Arcos and Matías Valdés-Peña and Juan J. de Pablo and Cristian Vilos and Ricardo A. Zamora and Ricardo Alessandri and Horacio Poblete},

doi = {10.1021/acs.nanolett.6c00637},

year  = {2026},

date = {2026-05-07},

journal = {Nano Letters},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{González-Avendaño2026,

title = {Computational Mapping and Targeting of BK Channel Protein–Protein Interactions in Breast Cancer},

author = {Mariela González-Avendaño and Roberto Rosales-Rojas and Ariela Vergara-Jaque },

doi = {10.1021/acs.jcim.6c00191},

year  = {2026},

date = {2026-03-17},

abstract = {Large-conductance Ca2+-activated potassium (BK) channels are widely expressed across human tissues and play fundamental roles in the regulation of diverse cellular processes. Dysregulation of BK channel expression or activity has been implicated in multiple pathological conditions, including cancer, where BK channel overexpression is associated with enhanced tumor cell proliferation and altered cellular dynamics. In this study, we present an integrative computational framework to identify, structurally characterize, and rationally target BK channel-associated protein–protein interactions (PPI) in breast cancer. RNA-seq differential expression analysis revealed significant overexpression of KCNMA1 in estrogen-sensitive breast cancer cells, supporting a central role for BK channels in tumor-associated phenotypes. By integrating transcriptomic data with curated interaction databases and PPI prediction methods, we constructed a breast cancer-specific interaction network centered on BK and identified ACTG2, LINGO1, and RAB4A as high-confidence interaction partners. Structural modeling and coarse-grained molecular dynamics simulations revealed stable, partner-specific interaction interfaces between BK and each interactor, identifying key residues governing complex formation. Building on these results, we present the first computational structural model of the BK-LINGO1 complex, which reveals a predominantly hydrophobic transmembrane interface consistent with the established role of LINGO1 as a regulatory accessory subunit. Leveraging this PPI interface, we designed peptide-based modulators using a structure-guided approach and identified peptide variants with enhanced conformational stability and favorable binding energetics. Overall, our work establishes a robust computational framework for mapping BK channel protein–protein interactions in breast cancer and demonstrates the feasibility of targeting these interactions through rational peptide design, opening new opportunities for the selective modulation of BK channel function in cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Peña-Vilches2026,

title = {Identification of 14-3-3 Proteins as Binding Partners of TRP Channels},

author = {Nicolás Peña-Vilches and Mariela González-Avendaño and Nicole Soto-García and Diego Maureira and Ian Silva and Javiera Avilés and Elías Manríquez-Benítez and Exequiel Medina and Oscar Cerda and Pablo Galaz-Davison and Ariela Vergara-Jaque},

doi = {10.1021/acs.jcim.6c00092},

year  = {2026},

date = {2026-03-16},

abstract = {Transient receptor potential (TRP) channels are regulated by a diverse network of intracellular partners that govern their trafficking, stability, and functional expression at the plasma membrane. Here, we present a comprehensive and integrative characterization of 14-3-3 proteins as conserved binding partners of TRP channels. Leveraging the extensive structural repertoire of 14-3-3 complexes resolved to date, we combined large-scale sequence and structural analyses with molecular docking, coevolutionary inference, machine learning-based predictions, atomistic simulations, and targeted experimental validation to elucidate the molecular principles underlying TRP-14-3-3 recognition. Integration of these approaches into a unified consensus scoring framework revealed recurrent, solvent-exposed cytoplasmic motifs across the TRP channel family with a high propensity for 14-3-3 binding. Focusing on the TRPM4-14-3-3γ interaction, we identified an N-terminal cytoplasmic region of the channel as the primary 14-3-3 binding hotspot. Structural modeling and molecular dynamics simulations revealed a stable electrostatically driven interface, which was experimentally validated by fluorescence anisotropy assays. Moreover, biochemical and functional analyses demonstrated that TRPM4 interacts not only with 14-3-3γ but also with 14-3-3η, leading to a reduced channel-mediated sodium influx. Together, these findings establish 14-3-3 proteins as general and evolutionarily conserved regulators of TRP channels and provide a broadly applicable framework for identifying transient protein–protein interactions relevant to TRP channel dysregulation in disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}