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Why do certain Covid variants infect you more than other? Or some antibodies are better in protecting you? Molecular interactions between oligomeric proteins like ACE2 or antibodies and the virus seem key, but have hitherto only been examined on a 1:1 interaction framework. Here a new methodology is presented which shines a light on the importance of cooperative interaction of all the processes in virus-host interaction and its neutralisation. This explains differences in SARS-CoV-2 infectivity and inhibition.

This paper by Jiri , Roi, Seham, Weston and Philipp demonstrates a substantial expansion in the application space of mass photometry through the combination of nanoparticle lithography with surface PEGylation, which results in a two orders of magnitude improvement in the upper concentration limit associated with mass photometry. Their artwork was chosen as cover art for NanoLetters 24 (33).

Myosin-5 carries cargoes inside cells by walking along helical F-actin filaments. Myosin-5 avoids walking helically by taking long steps equal to F-actin’s helical repeat. Previous measurements of step length show a broader spread of values than expected from the spatial resolution of the technique. We used iSCAT and electron microscopies, which have subnanometer precision, and find that the broad peak is really a family of narrow peaks that correspond to steps spanning different numbers of subunits along F-actin. We show that disorder within F-actin is the reason myosin-5 varies its step length because the F-actin subunit best oriented for walking in a straight line changes from step to step. Thus F-actin disorder has important impacts on cellular functions. This paper is the outcome of a longstanding collaboration between the Kukura group and NIH in Bethesda.

Scientists from our group have detected ultra-weak light scattering from single protein molecules using optical holography. Published in Nature Photonics, the new approach increases the sensitivity of the technique by five orders of magnitude compared to the current state of art. This breakthrough paves the way for a wider exploration of biomolecular interactions and applications in nanoscience.

One of the results of a 3 month sabbatical that Christian spent with us. New system, new science, new ideas - could not ask for more from a sabbatical. Thank you!

Jan's tour de force - where 9 years later we finally believe that the signals we see actually make sense, plus gives us lots of hope as to where MP can eventually go. And he answers probably the most often asked question after seminars: does shape matter? Well, a little bit...

One of our earliest collaborations using MP that turned into a much bigger and impressive story led by the Stetefeld group. Another great example of the importance of oligomerisation for a range of cellular processes.

And yet another paper that has emerged from a hugely productive visit by Chang to Oxford. Here, we used MP to help understand light-responsive RNA-protein nanowire switching and function.

A great collaboration with a number of groups from the Kavli Institute for Nanoscience Discovery. Excited to see that MP could help elucidate the role of lipids in the stability of bacterial outer membranes.

One of the most challenging studies this group has ever completed. What started out as a simple idea required years of improvement in instrumentation, completely new approaches to data analysis and the development of a new model to understand how actin polymerises. We think a first in terms of demonstrating what can be done with MP in the context of highly heterogeneous mixtures.

We have shown that a nano-sized spherical protein cage can undergo a major change in shape simply by changing a single amino acid. The work is interesting as it provides insight into how artificial protein containers can be engineered and molded into different shapes for different applications. It also is of interest from an evolutionary perspective: Typically, evolution is thought to occur gradually but this work is an example where major structural changes in large complexes come about from a single change.

We review recent advances in our ability to characterise biomolecular structure, interactions and associated dynamics by mass photometry (MP), the label-free detection and mass measurement of individual biomolecules in solution. Molecular counting and identification provides direct access to relative abundance, and thereby affinities, while associated dynamics yield on- and off-rates. The molecular resolution afforded by MP enables these measurements as a function of stoichiometry and assembly at equilibrium, as opposed to the majority of existing solution-based methods. Together with future improvements in terms of assays and technological performance, MP is likely to provide mechanistic details of complex biomolecular processes.

A collaboration that started on the blackboard after a talk in Bielefeld, involved a number of visits by Michael to Oxford and resulted in a great example how mass photometry can help with understanding polydispersity of proteins, and how that polydispersity relates to function.

It's not all about interferometric scattering. Darkfield, especially with super-optimised micromirrors is really, really awesome. If you are tracking metal nanoparticles, we think this is the way to go. And maybe even for molecules...

Wonderful work by the He group on designing protein nanoparticles to which we could contribute with mass photometry-based characterisation of protein oligomerisation.

Mass photometry unchained from microscope cover glass. Detection, imaging, tracking and mass measurement of membrane-associated complexes. In our opinion, the beginning of a new era for MP.

Jack and Lee really, really went all the way in terms of trying to provide an overview of scattering-based light microscopy on the nanoscale. Apologies to those we missed, but hopefully a good starting point for people getting going in this exciting field.

Yet another collaboration that started with "let's just have a look" where we could contribute to understanding the role of protein oligomerisation in R2TP with mass photometry.

An overview of light-based, label-free methods for studying how biomolecules interact. Our contribution is of course MP, but lots of amazing methods out there!

Started with a 5 minute chat after listening to Tim's amazing talk at the Klosters Winterseminar, and turned into an amazing story. Huge amount of work by the Clausen lab, with us contributing olgiomerisation dynamics - and surprises - at low concentration.

Just one of the papers the emerged from a sabbatical Sanli Faez from Uetrecht spent in Oxford - this one using single DNA molecules with gold particles attached to sense force on the nanoscale.

Another collaboration with IMP Vienna on proteasomal degradation mechanisms where we used mass photometry to help determine the stoichiometry and oligomerisation of LUBAC.