This Materials World Network project brings together Purdue University and the Universidad Autonoma de Madrid, Spain, to develop advanced Atomic Force Microscopy (AFM) techniques for investigating at high-resolution the material properties of viruses in relevant saline solutions. The goal is to enable significant advances in understanding viral function or its mitigation in medicine or in the synthesis of a new generation of nanomaterials using viruses for medicine, nanocomposites, sensors, and nanoelectronics. The proposed AFM techniques use novel multi-frequency techniques such as multi-harmonic or bimodal AFM which can provide compositional contrast in liquids far exceeding conventional methods at much faster speeds and with much greater sensitivity. The theory component of the proposed work attempts to distil metamodels from numerical simulations of mathematical models of AFM cantilevers tapping on samples in liquids, in order to link the observed material contrast to quantitative measures of local material properties. The experimental component of the proposal will investigate the inherent heterogeneities of elastic stiffness and charge density of the capsids of bacteriophages (phi 29 and T7) and eukaryotic viruses (minute virus of mice, and adenovirus) in solution and the influence of sub-surface DNA structure on the surface elasticity and charge of fully assembled viral capsids. The goal is to systematically investigate at high resolution the connection between DNA packing and capsid structure and the electromechanical properties of the assembled virus. An improved understanding of the structure-property-function relationships of viruses would not only broadly benefit medicine and virology, but it would also be a great boon to the many emerging applications of viruses in materials science and nanotechnology.
The project proposes to engage strongly with the materials and biophysics communities, AFM industries, and to the larger AFM materials community via cyber-enabled initiatives on the nanohub to ensure a wide ranging impact of the proposed work.
This award is co-funded by the Division of Materials Research and the Office of International Science and Engineering.
The Atomic Force Microscope (AFM) is a unique instrument that can image small biological ojects like viruses with extremely high resolution in their natural state, i.e. in aqueous solutions that mimic physiological conditions. This project has succeeded in adding one more dimension to this instruments' ability - that of simultaneously mapping physical properties like the elasticity and viscosity of the object being probed. The ability to simultaneously map the topography and physical properties at very high resolution (~ 1nm, which is 1/100,000 of the thickness of human hair) allows biophysicists and virologists to connect the internal structure of viruses and cells to their physical properties. In this project we have developed this novel imaging technique and used it to study two important problems. First we have shown that the mechanical properties of a breast cancer cell can change dramatically in unanticipated ways when expressing a tumor suppressing kinase. Secondly we have shown that DNA can escape from virions not only through the tail, but also through cracks or punctures of the viral shell. We expect this new imaging method to become an important tool in the emerging area of materials science of viruses, medical strategies for anti-viral drugs, and for the manufacture of nanomaterials using viruses for sensors, nanoelectronics, and nanocomposites far beyond applications in biology and medicine.
