Electrostatic Binding and Hydrophobic Collapse of Peptide-Nucleic Acid Aggregates Quantified Using Force Spectroscopy

• Main Authors: Camunas-Soler, Joan, Frutos, Silvia, Bizarro, Cristiano V, de Loreno, Sara, Fuentes-Perez, Maria Eugenia, Ramsch, Roland, Vilchez, Susana, Solans, Conxita, Moreno-Herrero, Fernando, Albericio, Fernando, Eritja, Ramon, Giralt, Ernest, Dev, Sukhendu B, Ritort, Felix
• Format: Journal Article
• Language: English
• Published: 05-08-2014
• Subjects: Physics - Biological Physics; Physics - Soft Condensed Matter; Quantitative Biology - Biomolecules
• DOI: 10.48550/arxiv.1408.1069

ACS Nano, 7 (2013) 5102-5113 Knowledge of the mechanisms of interaction between self-aggregating peptides
and nucleic acids or other polyanions is key to the understanding of many
aggregation processes underlying several human diseases (e.g. Alzheimer's and
Parkinson's diseases). Determining the affinity and kinetic steps of such
interactions is challenging due to the competition between hydrophobic
self-aggregating forces and electrostatic binding forces. Kahalalide F (KF) is
an anticancer hydrophobic peptide which contains a single positive charge that
confers strong aggregative properties with polyanions. This makes KF an ideal
model to elucidate the mechanisms by which self-aggregation competes with
binding to a strongly charged polyelectrolyte such as DNA. We use optical
tweezers to apply mechanical forces to single DNA molecules and show that KF
and DNA interact in a two-step kinetic process promoted by the electrostatic
binding of DNA to the aggregate surface followed by the stabilization of the
complex due to hydrophobic interactions. From the measured pulling curves we
determine the spectrum of binding affinities, kinetic barriers and lengths of
DNA segments sequestered within the KF-DNA complex. We find there is a capture
distance beyond which the complex collapses into compact aggregates stabilized
by strong hydrophobic forces, and discuss how the bending rigidity of the
nucleic acid affects such process. We hypothesize that within an in vivo
context, the enhanced electrostatic interaction of KF due to its aggregation
might mediate the binding to other polyanions. The proposed methodology should
be useful to quantitatively characterize other compounds or proteins in which
the formation of aggregates is relevant.