Michael A. Lynes Laboratory

Dr. Seth Fraden
Professor of physics, Brandeis University
Host: Carol Teschke

Symmetry-Guided Self-Assembly of DNA Origami and Proteins

We present a modular approach to synthetic self-assembly, using DNA and protein design to construct finite-sized nanostructures with a minimal number of unique monomers. Exploiting symmetry, we successfully assembled large icosahedral shells (100–1000 nm), inspired by Caspar and Klug’s 1962 virus structure theory. DNA origami enabled precise building block design, allowing us to control assembly pathways, kinetics, and yield. Cryo-EM validation and computational modeling revealed key factors governing self-assembly efficiency. These DNA-based capsids serve as an ideal realization of patchy particles whose geometry and interactions can be designed with sub-nanometer and kT precision. Expanding beyond icosahedra, we explored cylindrical and negatively curved surfaces. Now, leveraging AI-driven structure-based tools (Chroma, ESMfold, Boltz-1, AlphaFold3), we are testing whether these DNA origami principles apply to de novo protein design, pushing the frontiers of bioinspired materials engineering.

About Dr. Fraden:

Fraden is a professor of physics and co-interim chair of Engineering at Brandeis University, Waltham, MA. He served as director of the Bioinspired Soft Materials Research Science and Engineering Center (MRSEC) at Brandeis University from 2012 - 2024. Fraden received the 2008 Innovation Prize of the International Organization of Biological Crystallization for the development of microfluidic devices for high throughput protein crystallization. In 2020, Fraden was elected a Fellow of the American Physical Society for leadership in experimental soft matter physics. Fraden’s research focus is Bioinspired Soft Matter with a focus on (a) self-assembly in biomaterials with applications in antiviral therapy and drug delivery, (b) active matter with applications in soft robotics, (c) non-linear chemical dynamics and (d) the development of microfluidics for biotechnology with applications in protein crystallization.

Publications:

Economical routes to size-specific assembly of self-closing structures

Hierarchical assembly is more robust than egalitarian assembly in synthetic capsids

Programmable icosahedral shell system for virus trapping

Fraden website

John Briseno
Nyholm Lab