Mass photometry: a new technology platform for characterizing protein complexes

Affinity capture / mass spectrometry screening combined with mass photometry to asses sample heterogeneity and predict macromolecular topologies

Mass photometry can quickly reveal the compositions of mixtures of protein complexes – this technology has applications in biochemistry, structural biology, and pharmacology – these applications will be cooperatively explored in this partnership between Refeyn Ltd. and the Laboratory of Macromolecules and Interactomes at The European Research Institute for the Biology of Ageing, University Medical Center Groningen.

Presently, only ~1-2% of proteins are targeted by existing drugs. New druggable modalities are necessary and protein-protein interactions are new frontier in biomedicine because of this. To obtain the most relevant information concerning the molecular-level differences between health and disease, measurements should be made in the most native state possible – mass photometry offers improvements to address this possibility. When molecular-level differences between health and disease are observed, these provide actionable targets for developing new diagnostics and therapeutics. Combining mass photometry with other molecular techniques and proteomic technologies, like mass spectrometry, this research partnership will apply a suite of cutting-edge analyses to expedite how molecular-level differences between health and disease can be explored, defined, and ultimately targeted – expanding the druggable universe by extending it to protein-protein interactions.

Immunoprecipitation offers a method to extract protein complexes from cells and tissues – including, e.g., patient tumors and other clinical samples. Starting with this technique, mass photometry and can used to (1) assess the complexity of the samples obtained and (2) contribute to defining the differences in the macromolecules present healthy and diseased tissue samples. However, this approach comes with many challenges that this research and development project will explore and address.

Ultimately, we expect this research to result in a robust, portable, modular pipeline for exploring macromolecules and their differences in health and disease – empowering other biomedical researchers to conduct transformative explorations into how these differences can be exploited in the clinic.

In this research we explored the ability of mass photometry (MP) to provide a readout on the heterogeneity of macromolecular assemblies obtain by immunoprecipitation (IP). IP is a method by which macromolecular assemblies can be retrieved from endogenous sources and may therefore faithfully report on e.g., pathobiological or drug-induced changes in such assemblies.

Summary

Mass photometry is a new technology for measuring the masses of protein complexes in solution. A key feature of this technology is its ability to readout collections of masses present in mixtures that might otherwise be difficult to measure by other methods, creating new analytical possibilities.

Technology Readiness Level (TRL)

3 - 4

Time period

48 months

Partners