title: A quantitative recipe for engineering protein polymer nanoparticles.
abstract: Protein polymers can assemble switchable nanostructures with emerging applications as biomaterials and nanomedicines. For example, above a critical micelle temperature (CMT) some elastin-like polypeptide (ELP) diblock copolymers assemble spherical nanoparticles, which may modulate cellular internalization andin vivobiodistribution. To achieve engineering-level control over their properties, this report explores a comprehensive library of ELP monoblock and diblock polymers. For the first time, we report that a surprisingly high core molecular weight is required for stable nanoparticle formation; furthermore, nanoparticle size depends on polymer molecular weight. A mathematical model was developed to characterize four ELP monoblock libraries and to predict the phase behavior of corresponding diblock copolymers. The CMT was almost entirely dependent on the hydrophobic core ELP, while the bulk phase transition temperature (Tt,bulk) depends predominantly on the hydrophilic block. Nanoparticle assembly was accompanied by a conversion in secondary structure of the hydrophobic block from random coil and beta-sheets to type-2 β turns. For the first time, this report enables the rational design of ELP protein polymer nanoparticles with physico-chemico properties that will be suitable for biological applications.
authors: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA; 90033-9121.
authors: S Mohd
authors: SM
authors: Janib
authors: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA; 90033-9121.
authors: M
authors: M
authors: Pastuszka
authors: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA; 90033-9121.
authors: S
authors: S
authors: Aluri
authors: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA; 90033-9121.
authors: Z
authors: Z
authors: Folchman-Wagner
authors: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA; 90033-9121.
authors: P-Y
authors: PY
authors: Hsueh
authors: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA; 90033-9121.
authors: P
authors: P
authors: Shi
authors: Department of Chemical and Biomolecular Engineering, Johns Hopkins University Baltimore, MD 21218 USA.
authors: Yi-An
authors: Department of Chemical and Biomolecular Engineering, Johns Hopkins University Baltimore, MD 21218 USA.
authors: H
authors: H
authors: Cui
authors: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA; 90033-9121.
authors: J A
authors: JA
authors: Mackay
keywords: Elastin-like polypeptide; block copolymer; micelles; self-assembly