3D Nano-printing of protein nanostructures using DNA molds
Abstract
One of the key goals in bionanotechnology is to develop materials that can mimic the remarkable structures and functions of biological system. Proteins are the most versatile of all biological building blocks, with a vast array of functions as diverse as structural support, molecular signaling, force generation, and highly precise catalysis. However, it is still not possible to design complex nanostructures out of proteins that can rival those in natural cells. The reason for this is that researchers still do not understand the relationship between protein sequence and complex 3D structures (formed through self-assembly) with sufficient precision. DNA nanotechnology, by contrast, uses the orthogonality of base pairing to construct highly elaborate nanostructures from oligonucleotide strands. In this proposal, we aim to use a DNA nanoscaffold to position proteins with a degree of control not possible through protein assembly alone. We will modify a series of highly stable proteins with DNA handles, allowing them to be attached to a DNA “mold” with nanometer precision. Chemically linking these proteins and then removing them from the mold will generate an all-protein nanostructure. However, because each protein-DNA brick (or “p-brick”) can be unique, we can design nanostructures with unprecedented complexity. We will explore two- and three-dimensional “3D nano-printing” of structures with this approach, and design several nanostructures that highlight the powers of this method. We will also append functional proteins to these p-bricks, paving the way for various applications, including: novel biomaterials, synthetic antibodies and viruses, molecular machines, and new biosensors. Ultimately, our method can be extended to any protein, in principle, paving the way for truly user-defined, complex protein nanomaterials that can mimic, and perhaps surpass, those in biological systems.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 21, 2022
- Source ID
- FA95502110210XX0
Entities
People
- Nicholas Stephanopoulos
Organizations
- Air Force Office of Scientific Research
- United States Air Force