Just as the advent of single-cell sequencing revolutionized genomics, Depixus MAGNA One™ is set to transform the field of interactomics. Built on magnetic force spectroscopy, this groundbreaking instrument enables unprecedented insights into thousands of individual biomolecular interactions.

Breakthroughs in biology are driven by technological advances in scale and resolution

Over the past two decades, we have seen major breakthroughs in our understanding of biology and the development of novel therapeutics. Many of these breakthroughs have been driven by exponential advances in the scale and resolution of biomolecular measurements.

In genomics, for example, technological innovations have led to a 10,000-fold increase in the scale of DNA and RNA sequencing.¹ These advances, combined with improvements in liquid handling and automation, have enabled the development of single-cell genomics and transcriptomics.^2,3

For instance, single-cell RNA sequencing (scRNA-seq) now allows researchers to analyze millions of cells with unprecedented resolution, uncovering significant heterogeneity within tissues.^2,4 This has provided transformative insights into cancer biology, such as identifying rare cell states and mechanisms of resistance to therapies.²

Similarly, the scale and resolution of proteomics has advanced dramatically, allowing researchers to precisely measure thousands of individual biomarkers in tissues and plasma, including rare isoforms.

Recent advancements in single-cell proteomics have made it possible to identify a vast array of proteins in individual cells, significantly improving our understanding of cellular biology.⁵ These innovations have expanded our understanding of biological complexity and are driving the discovery of novel drug targets.

In the same way that single-cell sequencing and advances in proteomics have transformed our understanding of genomes and proteomes, Depixus MAGNA One represents a new frontier in our ability to study how individual molecules interact at unprecedented scale.

Studying the interactome is challenging

Life runs on a complex network of interactions between biological molecules, such as DNA, RNA, proteins, lipids and more.

These interactions make up what is known as the interactome. Understanding and measuring these interactions is key to our understanding of health and disease, and the development of more effective therapeutics – see Figure 1 for an example of the complex interactome related to schizophrenia.

Figure 1: A graphical representation of the complexity of the schizophrenia interactome, with genes as nodes and protein-protein interactions as edges connecting the nodes. Taken from Ganapathiraju, et al. (2016)⁶ CC BY 4.0

However, analyzing these interactions is a challenge. Not all biomolecules are equal, nor are all interactions.

Heterogeneity among biomolecules means that even nominally identical proteins or nucleic acids may differ due to different chemical modifications or structural conformations that affect their activity and function. Similarly, interactions that are biologically relevant may be relatively weak, rare, and/or transient, complicating their detection and study.

Up until now, researchers have used a combination of approaches to understand and measure biomolecular interactions, ​each with its own limitations.

Depixus MAGNA One addresses these limitations, offering an accessible analytical technology that can measure the dynamics of individual biomolecular interactions at a scale of thousands of molecules.

Depixus MAGNA One analyzes individual dynamic biomolecular interactions at scale

Depixus MAGNA One is built on ​magnetic force spectroscopy (MFS) technology, which directly measures the forces at work as molecules interact. However, in traditional magnetic tweezer MFS approaches, the number of interactions that can be analyzed at any one time is limited.⁷

With Depixus MAGNA One, we’ve developed a way to scale this up, capturing dynamic measurements from thousands of individual biomolecular interactions in parallel.

This data reveals key biophysical parameters and provides mechanistic insights into how binding proteins, small molecules, or other ligands impact molecular interactions, including detailed information about binding kinetics.

By analyzing individual biomolecular interactions at scale, Depixus MAGNA One allows the detection of heterogeneity and rare or transient interactions, providing a deeper understanding of fundamental biological processes and advancing drug development.

The platform’s versatility supports applications across a wide range of biomolecules (e.g. DNA, RNA, proteins and small molecules). This makes Depixus MAGNA One particularly valuable for studying emerging therapeutic targets and modalities, such as RNA-targeted drugs, molecular glues and protein-protein interactions (PPIs).

The value of single molecule interactomics in drug development

The ability of Depixus MAGNA One to analyze individual biomolecular interactions at scale has particular utility in drug development at the hit-to-lead stage, where biophysical methods are used to assess whether candidate compounds bind their target and have the desired mechanism of action, along with detailed measurements of the kinetics, thermodynamics and stoichiometry of binding.

Taking the example of RNA-targeted drug development, our magnetic force spectroscopy technology was used in collaboration with Dr. Jay Schneekloth to investigate interactions between the PreQ₁ bacterial riboswitch – an attractive novel antibacterial drug target – and its natural ligand, as well as a synthetic small molecule.

Published in Nature Communications, the single molecule insights we provided revealed that the two ligands stabilized the folded riboswitch structure through distinct mechanisms, which would not have been detectable using bulk analytical methods.

By providing unprecedented in-depth single molecule insights like these, Depixus MAGNA One allows researchers to see what’s really happening as their drug engages its target (or not). In turn, this supports more robust hit-to-lead selection and optimization, reducing the chances of failure later in the drug development journey.

Depixus MAGNA One aims to transform the field of interactomics

Depixus MAGNA One represents a transformative leap forward, bringing large-scale, single-molecule resolution to the fast-growing science of interactomics.

By making it possible to see biology as it really happens, Depixus aims to do for single molecule interactomics what companies like 10x Genomics did for single cell genomics: open up a new field of study, accelerate our understanding of disease, and enable the development of novel therapeutics.

To learn more about the groundbreaking capabilities of Depixus MAGNA One and how it can revolutionize your research, check out our detailed product brochure.

References

1. Satam H, et al. Next-Generation Sequencing Technology: Current Trends and Advancements. Biology. 2023 Jul 1;12(7):997. doi: 10.3390/biology12070997
2. Cuomo ASE, Nathan A, Raychaudhuri S, MacArthur DG, Powell JE. Single-cell genomics meets human genetics. Nat Rev Genet. 2023 Aug;24(8):535-549. doi: 10.1038/s41576-023-00599-5.
3. Aldridge S, Teichmann SA. Single cell transcriptomics comes of age. Nat Commun. 2020 Aug 27;11(1):4307. doi: 10.1038/s41467-020-18158-5
4. Han X, et al. Construction of a human cell landscape at single-cell level. Nature. 2020 Mar 25;581(7808):303–9. doi: 10.1038/s41586-020-2157-4
5. Ahmad R, Budnik B. A review of the current state of single-cell proteomics and future perspective. Analytical and Bioanalytical Chemistry. 2023 Jun 7;415(28):6889–99. doi: 10.1007/s00216-023-04759-8
6. Ganapathiraju MK, Thahir M, Handen A, Sarkar SN, Sweet RA, Nimgaonkar VL, et al. Schizophrenia interactome with 504 novel protein–protein interactions. npj Schizophrenia. 2016 Apr 27;2(1). doi: 10.1038/npjschz.2016.12
7. Dulin, D. (2024). An Introduction to Magnetic Tweezers. Methods in Molecular Biology (Clifton, N.J.), [online] 2694, pp.375–401 doi: 10.1007/978-1-0716-3377-9_18