COVID-19 remains an ongoing issue across the globe, highlighting the need for a rapid, selective, and accurate sensor for SARS-CoV-2 and its emerging variants. The chemical specificity and signal amplification of surface-enhanced Raman spectroscopy (SERS) could be advantageous for developing a quantitative assay for SARS-CoV-2 with improved speed and accuracy over current testing methods. Here, we have tackled the challenges associated with SERS detection of viruses. As viruses are large, multicomponent species, they can yield different SERS signals, but also other abundant biomolecules present in the sample can generate undesired signals. To improve selectivity in complex biological environments, we have employed peptides as capture probes for viral proteins and developed an angiotensin-converting enzyme 2 (ACE2) mimetic peptide-based SERS sensor for SARS-CoV-2. The unique vibrational signature of the spike protein bound to the peptide-modified surface is identified and used to construct a multivariate calibration model for quantification. The sensor demonstrates a 300 nM limit of detection and high selectivity in the presence of excess bovine serum albumin. This work provides the basis for designing a SERS-based assay for the detection of SARS-CoV-2 as well as engineering SERS biosensors for other viruses in the future.

The native extracellular matrix communicates and interacts with cells by dynamically displaying signals to control their behavior. Mimicking this dynamic environment in vitro is essential in order to unravel how cell–matrix interactions guide cell fate. Here, we present a synthetic platform for the temporal display of cell-adhesive signals using coiled-coil peptides. By designing an integrin-engaging coiled-coil pair to have a toehold (unpaired domain), we were able to use a peptide strand displacement reaction to remove the cell cue from the surface. This allowed us to test how the user-defined display of RGDS ligands at variable duration and periodicity of ligand exposure influence cell spreading degree and kinetics. Transient display of αVβ3-selective ligands instructed fibroblast cells to reversibly spread and contract in response to changes in ligand exposure over multiple cycles, exhibiting a universal kinetic response. Also, cells that were triggered to spread and contract repeatedly exhibited greater enrichment of integrins in focal adhesions versus cells cultured on persistent RGDS-displaying surfaces. This dynamic platform will allow us to uncover the molecular code by which cells sense and respond to changes in their environment and will provide insights into ways to program cellular behavior.

A new class of hybrid biomaterials has recently evolved from the combination of peptides and DNA. In this chapter, we survey the unique systems and properties made possible by merging the bioactivity and mechanical properties of peptides with the programmability and reversibility of DNA. We explore peptide–DNA probes and switches, peptide-decorated DNA scaffolds and DNA-decorated peptide structures. We illustrate the rich variety of architectures made from the interplay of orthogonal peptide and DNA assembly motifs in cooperative assemblies, with examples of peptide-directed or DNA-directed hybrid structures. We present systems with hierarchical organization and dynamic assembly, presenting fascinating emergent properties made possible by peptide–DNA combinations. Finally, we discuss the future possibilities and open challenges presented by this intriguing class of hybrid biomaterials.

Translating sensors from the lab benchtop to a readily available point-of-need setting is desirable for many fields, including medicine, agriculture, and industry. However, this transition generally suffers from loss of...