Photocrosslinkable Unnatural Amino Acids Enable Facile Synthesis of Thermoresponsive Nano- to Micro-gels of Intrinsically Disordered Polypeptides

摘要

Hydrogel particles are versatile materials that provide exquisite, tunable control over the sequestration and delivery of materials in pharmaceutics, tissue engineering, and photonics. The favorable properties of hydrogel particles depend largely on their size, and particles ranging from nanometers to micrometers are used in different applications. Previous studies have only successfully fabricated these particles in one specific size regime and required a variety of materials and fabrication methods. We have developed a simple yet powerful system to easily tune the size of polypeptide-based, thermoresponsive hydrogel particles, from the nano to microscale, using a single starting material. We take advantage of the self-assembly and unique phase transition behavior of elastin-like polypeptides (ELPs) in bulk and within microfluidic-generated droplets to control particle size. These particles are then stabilized through ultraviolet irradiation of a photocrosslinkable unnatural amino acid (UAA) cotranslationally incorporated into the parent polypeptide. The thermoresponsive property of these particles provides an active mechanism for actuation and a dynamic responsive to the environment. This work represents a fundamental advance in the generation of crosslinked biomaterials, especially in the form of soft matter colloids, and is the one of the first demonstrations of successful use of UAAs in generating a novel material.