Designed Biopolymers

Design of self-assembling protein-DNA hybrid nanomaterials

Currently DNA nanotechnology is the only way of creating truly nm-scale addressable nanostructures, but these structures are fundamentally limited in size, currently <100 nm or smaller. We believe that by combining it with proteins we can make higher order biocompatible and addressable nanomaterials of arbitrary shapes and sizes >100 nm. In this project we are computationally designing de-novo repetitive proteins that fully cover and protect template DNA, while still allowing for addressable sites by using sequence specific binders. Ultimately design of such DNA-protein hybrid materials will allow us to create addressable nanomaterials with various applications in nanotechnology and biomedicine. For example, in collaboration with the King lab (University of Washington), we intend to explore the ability to program antigens on the surface of these new nanomaterials for antigen display.

Contact
Rob de Haas – rob.dehaas@wur.nl

Templated assembly of DNA by proteins. Binding occurs through electrostatic interactions in the major groove of DNA. Proteins self-assemble on the DNA template through DNA-protein and protein-protein interaction to form tightly packed fibers.
Atomic Force Microscopy image of dried protein-DNA fibers

Design of ice-binding proteins

Ice-binding proteins are present in some artic plants and bacteria to prevent nucleation of ice crystals. Binding of these proteins to ice lowers the freezing point, which allows these organims to survive in sub-zero temperatures. We are attempting to re-engineer natural ice-binding proteins to increase ice-affinity and stabilize the protein structures. Ultimately these improved ice-binding proteins have applications cryo-surgery, organ transplantation and the food industry.

Contact
Rob de Haas – rob.dehaas@wur.nl
(design & characterization)

Chuanbao Zheng – chuanbao.zheng@wur.nl
(computer simulations)

A pdb model of an idealized ice-binding protein. Each repeat contains 2 threonine’s, which bind the basal and primary-prism planes of ice crystals.
Design of Polypeptide linkers for biosensing

Biosensors are becoming increasingly relevant both in research and diagnostics. Most biosensing tools exploit antibodies adsorbed on a surface like silica or plastic, in order to detect an analyte of interest. Although cheap and fast, this process is unfortunately also very inefficient. The current alternatives require expensive and complicated treatments of the biosensor surface. In this project, we focus on the design of polypeptide linkers to functionalize biosensor surfaces. In fact, naturally-occurring protein polymers can be easily engineered and tuned in their physical properties. The polypeptide linkers should be able to provide a stable and anti-fouling polymer brush, on which antibodies can be covalently attached. In collaboration with the department of Organic Chemistry, many polypeptide designs are screened and tested in order to find a suitable candidate. The linkers can be directly applied to newly designed biosensors from our collaborators at the Eindhoven University of Technology (de Jong lab).

Contact
Nicolò Alvisi – nicolo.alvisi@wur.nl

Schematic representation of the polymer brush monomers
Design of structural surface binding proteins

Many natural proteins exist that bind to solid-liquid interfaces such as to ice crystals, or to mineral surfaces such as hydroxyapatite (bone) or calcium carbonate (shells). Inspired by these proteins, we work on designing structural proteins that bind to solid-liquid interfaces relevant in technology, such as metal surfaces or plastic surfaces to act as interfaces between man-made devices and biological fluids, cells, and tissues.

Contact
Chuanbao Zheng – chuanbao.zheng@wur.nl
Rob de Haas – rob.dehaas@wur.nl

A pdb model of a de-novo designed protein where one side contains only positively charged (arginine) amino acids, that can bind negatively charged surfaces like silica through electrostatic interactions.