Resolving Structure and Mechanical Properties at the Nanoscale of Viruses with Frequency Modulation Atomic Force Microscopy

David Martinez-Martin, Autonomous University of Madrid
Carolina Carrasco, Autonomous University of Madrid; Consejo Superior de Investigaciones Cientificas (CSIC)
Mercedes Hernando-Perez, Autonomous University of Madrid
Pedro J. de Pablo, Autonomous University of Madrid
Julio Gomez-Herrero, Autonomous University of Madrid
Rebeca Perez, Consejo Superior de Investigaciones Cientificas (CSIC)
Mauricio G. Mateu, Consejo Superior de Investigaciones Cientificas (CSIC)
Jose L. Carrascosa, Consejo Superior de Investigaciones Cientificas (CSIC)
Daniel Kiracofe, Birck Nanotechnology Center, Purdue University
John Melcher, Birck Nanotechnology Center, Purdue University
Arvind Raman, Birck Nanotechnology Center, Purdue University

Date of this Version

1-25-2012

Citation

Martinez-Martin D, Carrasco C, Hernando-Perez M, de Pablo PJ, Gomez-Herrero J, Perez R, et al. (2012) Resolving Structure and Mechanical Properties at the Nanoscale of Viruses with Frequency Modulation Atomic Force Microscopy. PLoS ONE 7(1): e30204. doi:10.1371/journal.pone.0030204

Comments

© 2012 Martinez-Martin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Structural Biology (SB) techniques are particularly successful in solving virus structures. Taking advantage of the symmetries, a heavy averaging on the data of a large number of specimens, results in an accurate determination of the structure of the sample. However, these techniques do not provide true single molecule information of viruses in physiological conditions. To answer many fundamental questions about the quickly expanding physical virology it is important to develop techniques with the capability to reach nanometer scale resolution on both structure and physical properties of individual molecules in physiological conditions. Atomic force microscopy (AFM) fulfills these requirements providing images of individual virus particles under physiological conditions, along with the characterization of a variety of properties including local adhesion and elasticity. Using conventional AFM modes is easy to obtain molecular resolved images on flat samples, such as the purple membrane, or large viruses as the Giant Mimivirus. On the contrary, small virus particles (25-50 nm) cannot be easily imaged. In this work we present Frequency Modulation atomic force microscopy (FM-AFM) working in physiological conditions as an accurate and powerful technique to study virus particles. Our interpretation of the so called "dissipation channel'' in terms of mechanical properties allows us to provide maps where the local stiffness of the virus particles are resolved with nanometer resolution. FM-AFM can be considered as a non invasive technique since, as we demonstrate in our experiments, we are able to sense forces down to 20 pN. The methodology reported here is of general interest since it can be applied to a large number of biological samples. In particular, the importance of mechanical interactions is a hot topic in different aspects of biotechnology ranging from protein folding to stem cells differentiation where conventional AFM modes are already being used.

Discipline(s)

Nanoscience and Nanotechnology

 

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