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Francesca Santoro1 2 Bianxiao Cui2

1, Istituto Italiano di Tecnologia, Napoli, , Italy
2, Stanford University, Stanford, California, United States

The interface between biological cells and non-biological materials has profound influences on cellular activities, chronic tissue responses, and ultimately the success of medical implants and bioelectronic devices. Materials in contact with cells can be metals, plastics, silicon, ceramics or other synthetic materials, and their surfaces vary widely in chemical compositions, stiffness and levels of roughness. In particular, the interaction of cells with diverse materials relies primarily on the specific adhesion of the plasma membrane on to the material surface. Many attempts have been carried out in the last decade for characterizing this interface, however major limitations have been presented in respect to resolution and artefacts introduced by typical substrate removal. Here, we present an advanced microscopy method (scanning electron microscopy/focused ion beam) based on ultra-thin resin plastificization which uniquely allows the visualization of the interface between cells and materials with 5-10 nm resolution(Santoro et al., 2017; Zhao et al., 2017). Furthermore, we prove that this method can be used for organic and inorganic 2D materials, planar substrates with 3D vertical features (Santoro et al., 2017b, Cui et al., 2018) of different shapes and ultimately 3D scaffold-like systems (Mollo et al., 2018).

References
Cui B., McGuire A., Santoro F., Interfacing Cells with Vertical Nanoscale Structures: Applications and Characterization, Annual Review of Analytical Chemistry, 2018-accepted.
Mollo V., Iandolo D., Pennacchio F., Rossi D., Dannhauser D., Langella A., Netti P., Cui B., Owens R., Santoro F., (in preparation). Nanoscale resolution of 3D scaffold- cell interaction by SEM/FIB, in preparation.
Santoro, F., Zhao, W., Joubert, L.-M., Duan, L., Schnitker, J., van de Burgt, Y., Lou, H.-Y., Liu, B., Salleo, A., Cui, L., Cui Y., Cui B., Revealing the Cell–Material Interface with Nanometer Resolution by Focused Ion Beam/Scanning Electron Microscopy. ACS Nano, 2017.
Santoro, F., Van der Burgt Y., Keene S. T., Cui B., Salleo A., Enhanced cell–chip coupling by rapid femtosecond laser patterning of soft PEDOT: PSS biointerfaces.. ACS Applied Materials and Interfaces, 2017.
Zhao, W., Hanson, L., Lou, H.-Y., Akamatsu, M., Chowdary, P.D., Santoro, F., Marks, J.R., Grassart, A., Drubin, D.G., Cui, Y., Cui B., Nanoscale manipulation of membrane curvature for probing endocytosis in live cells. Nature Nanotechnology, 2017.

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