Quantitative mass imaging of single biological macromolecules.
Gavin YoungNikolas HundtDaniel ColeAdam FinebergJoanna AndreckaAndrew TylerAnna OlerinyovaAyla AnsariErik G MarklundMiranda P CollierShane A ChandlerOlga TkachenkoJoel D AllenMax CrispinNeil BillingtonYasuharu TakagiJames R SellersCédric EichmannPhilipp SelenkoLukas FreyRoland RiekMartin R GalpinWeston B StruweJustin L P BeneschPhilipp KukuraPublished in: Science (New York, N.Y.) (2018)
The cellular processes underpinning life are orchestrated by proteins and their interactions. The associated structural and dynamic heterogeneity, despite being key to function, poses a fundamental challenge to existing analytical and structural methodologies. We used interferometric scattering microscopy to quantify the mass of single biomolecules in solution with 2% sequence mass accuracy, up to 19-kilodalton resolution, and 1-kilodalton precision. We resolved oligomeric distributions at high dynamic range, detected small-molecule binding, and mass-imaged proteins with associated lipids and sugars. These capabilities enabled us to characterize the molecular dynamics of processes as diverse as glycoprotein cross-linking, amyloidogenic protein aggregation, and actin polymerization. Interferometric scattering mass spectrometry allows spatiotemporally resolved measurement of a broad range of biomolecular interactions, one molecule at a time.