Influenza A matrix protein M1 multimerizes upon binding to lipid membranes

Biophys J. 2014 Aug 19;107(4):912-23. doi: 10.1016/j.bpj.2014.06.042.


The matrix protein M1 plays a pivotal role in the budding of influenza virus from the plasma membrane (PM) of infected cells. This protein interacts with viral genetic material and envelope proteins while binding to the inner leaflet of the PM. Its oligomerization is therefore closely connected to the assembly of viral components and the formation of new virions. Of interest, the molecular details of M1 interaction with lipids and other viral proteins are far from being understood, and it remains to be determined whether the multimerization of M1 is affected by its binding to the PM and interaction with its components. To clarify the connection between M1 oligomerization and binding to lipid membranes, we applied a combination of several quantitative microscopy approaches. First, we used number and brightness (N&B) microscopy to characterize protein multimerization upon interaction with the PM of living cells. Second, we used controlled biophysical models of the PM (i.e., supported bilayers) to delve into the details of M1-lipid and M1-M1 interactions by employing a combination of raster image correlation spectroscopy (RICS), fluorescence correlation spectroscopy (FCS), and atomic force microscopy (AFM). Our results show that M1 oligomer formation is strongly enhanced by membrane binding and does not necessarily require the presence of other viral proteins. Furthermore, we propose a specific model to explain M1 binding to the lipid bilayer and the formation of multimers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / metabolism*
  • Dogs
  • Influenza A virus
  • Lipid Bilayers / metabolism*
  • Madin Darby Canine Kidney Cells
  • Microscopy / methods
  • Models, Biological
  • Protein Multimerization
  • Spectrum Analysis / methods
  • Viral Matrix Proteins / metabolism*


  • Lipid Bilayers
  • M1 protein, Influenza A virus
  • Viral Matrix Proteins