title: Nanomechanical mapping of first binding steps of a virus to animal cells.
abstract: Viral infection is initiated when a virus binds to cell surface receptors. Because the cell membrane is dynamic and heterogeneous, imaging living cells and simultaneously quantifying the first viral binding events is difficult. Here, we show an atomic force and confocal microscopy set-up that allows the surface receptor landscape of cells to be imaged and the virus binding events within the first millisecond of contact with the cell to be mapped at high resolution (<50 nm). We present theoretical approaches to contour the free-energy landscape of early binding events between an engineered virus and cell surface receptors. We find that the first bond formed between the viral glycoprotein and its cognate cell surface receptor has relatively low lifetime and free energy, but this increases as additional bonds form rapidly (≤1 ms). The formation of additional bonds occurs with positive allosteric modulation and the three binding sites of the viral glycoprotein are quickly occupied. Our quantitative approach can be readily applied to study the binding of other viruses to animal cells.
authors: ETH Zürich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.|Université Catholique de Louvain, Institute of Life Sciences, 1348 Louvain-La-Neuve, Belgium.
authors: David
authors: 0000-0001-9229-113X
authors: D
authors: Alsteens
authors: ETH Zürich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
authors: Richard
authors: R
authors: Newton
authors: ETH Zürich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
authors: Rajib
authors: R
authors: Schubert
authors: ETH Zürich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
authors: David
authors: D
authors: Martinez-Martin
authors: Université Catholique de Louvain, Institute of Life Sciences, 1348 Louvain-La-Neuve, Belgium.
authors: Martin
authors: M
authors: Delguste
authors: Friedrich Miescher Institute (FMI), 4058 Basel, Switzerland.|Department of Ophthalmology, University of Basel, 4056 Basel, Switzerland.
authors: Botond
authors: B
authors: Roska
authors: ETH Zürich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
authors: Daniel J
authors: DJ
authors: Müller
mesh_terms: D000818:Animals; D006224:Cricetinae; D004285:Dogs; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D018613:Microscopy, Confocal; D011820:Rabies virus / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D006023:Glycoproteins; D014764:Viral Proteins