Events

Evolutionary changes in the host-virus interactome can alter the course of infection, but which and how often interactions evolve and how this is realized at the interface residue level, remain largely unexplored. Here, we focus on viral mimicry of motifs and domains of host proteins, that allow efficient binding to host proteins by mimicking interfaces of host proteins. Our results show that in contrast to the prevailing view of rapid interface evolution between host- and viral-interacting proteins, viruses evolved to target highly conserved host proteins. The similarity between viral mimics and their host mimicked proteins limits host capacity to escape interaction with mimics, enabling efficient viral interaction with host targets through mimicry. These results have important implications for our understanding of zoonotic events where novel host-virus protein interactions may evolve and for designing new antiviral drugs targeting interface regions between host and viral proteins.

Synthetic chemistry has enabled the creation of materials with remarkable properties, yet they often lack the

dynamic nature exhibited by biological systems. In contrast, living matter is self-organizing and responsive, which

is critical for processes such as cell differentiation, sensing, transport, actuation, structural support, and—more

broadly—adaptation to internal and external stimuli. Intriguingly, the application of DNA nanotechnology to

synthetic materials has opened avenues for achieving a range of features and a level of control reminiscent of

biological systems. These materials have begun to emulate key cellular mechanisms, including the modulation of

viscoelastic properties in the extracellular matrix, cytoskeletal shape changes, control of molecular transport, and

the localization of processes in biomolecular condensates. In this talk, I will describe our progress in developing

such programmable materials and highlight two recent examples. First, I will introduce a novel precision matrix for

culturing cells and organoids. By integrating customizable mechanics with predictable, responsive features, this

matrix both guides and probes cellular development. Second, I will present an exotic form of soft matter that is

self-assembled from more than 16,000 unique molecular components. This material demonstrates that high

compositional complexity can yield unique molecular architectures with emergent properties distinct from those

of conventional polymers.

References:

* Speed et al. J. Polym. Sci. 2023, 61, 1713.

* Peng et al., Nature Nanotech. 2023, 18, 1463.

* Krieg & Shih, Angew. Chem. Int. Ed. 2018, 57, 714.

* Gupta & Krieg, Nucl. Acids Res. 2024, 52, e80.

* Prakash et al., Nature Nanotech. 2021, 16, 2021.

* Speed et al., BioRxiv 2024. https://doi.org/10.1101/2024.07.12.603212

Hard coatings are integral to modern manufacturing, significantly impacting the optical properties, friction, hardness,

corrosion resistance, and wear resistance of various surfaces. The global market for hard coatings is valued at $1.2 billion,

with strong growth expected in the coming years, offering opportunities for the direct application of fundamental

research in industrial settings. One key challenge in this field is the low toughness of protective coatings, particularly in

nitrogen-based PVD/CVD hard coatings, where this issue is compounded by the low cohesive energy of grain boundaries.

Due to their lack of ductility, nitrogen-based ceramic materials are prone to grain boundary cracking under mechanical

load, leading to the degradation of protective layers and reduced lifetime of coated parts. Our research focuses on

understanding the structure-property relationships of these materials.

Commercial coatings are typically a few micrometers thick, with microstructures consisting of grains ranging from

nanometers to micrometers, making them well-suited for study using modern electron microscopy. By combining

picoindentors for in situ SEM and TEM with FIB-based manufacturing, we developed in situ testing approaches to assess

key mechanical properties such as Young's modulus, fracture stress, and fracture toughness, as well as to explore the

underlying fracture mechanisms. In this talk, I will present our findings on the design of grain boundaries, material

composition, and transformation toughening strategies, which have significantly enhanced the mechanical properties of

hard coatings.

In nature, sequence-specific biopolymers, such as peptides and nucleic acids, are essential to various biological systems and processes. These biopolymers are utilized in materials science to achieve precise property control. Typically, variations in amino acid sequences focus on functional regulation while nucleotides are used for structural control. This raises the question: How can we integrate peptide-based functionality with the spatial precision of DNA nanotechnology for innovative material design? Here, I will present examples illustrating the incredible properties of peptide self-assembly from my PhD, and the remarkable nanoarchitecture design achieved through DNA nanotechnology from my Postdoc. These two key elements establish a vision of utilizing and synergizing peptide functionality with structural control achieved by DNA nanotechnology.

Specifically, I will show how subtle changes in the molecular environment influence the morphology and behavior of peptide assemblies such as diphenylalanine crystals and enable control over their growth and disassembly processes, revealing insights into peptide-based material manipulation (Nat. Commun., 2016). Another example is that of the amorphous assemblies of tri-tyrosine peptides, where we linked the molecular arrangement to unique mechanical and optical properties of glass-like peptide structures (Nature, 2024).

Next, I will introduce the principles of DNA nanotechnology for advanced structural control. By designing DNA nano-frames capable of self-assembling into organized lattices, we created micron-scale 3D materials. We discovered that a minor modification in DNA linker length induces a crystalline phase transition, from simple cubic to face-centered cubic structures, altering lattice geometry. In addition, we established a method using acoustic waves to achieve scalable and morphologically controllable DNA assemblies at the millimetric scale (Nat. Commun., 2024). This approach highlights how DNA nanotechnology provides unparalleled spatial control, decoupling structural architecture from functional elements such as peptides and nanoparticles. Together, these projects illustrate how peptides and DNA nanotechnology can be potentially integrated to engineer novel materials and enhance our capacity to design materials with tailored properties across scales.