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Project C1: Exploring the interactions between biological systems and patterned surfaces at the micro- and nanoscale

Principal Investigators: J. Rühe (Freiburg) / M.-P. Krafft (Strasbourg) / K. Anselme (Mulhouse)
PhD Student: Melanie Eichhorn

Current state of the research

Control of the cell adhesion to artificial surfaces is a critical factor for the biocompatibility of materials and determines their usefulness in many medical applications, especially of medical implants. Accordingly, large research efforts have been devoted to generate biomaterials, i.e. materials in contact with biological systems, which show a favorable interaction with biological cells. Next-generation-device biomaterials require that much more complex and/or multifunctional surfaces need to be developed because the surfaces of the involved material control all the interactions with the environment. The influence of the surfaces onto cells can be divided into three classes:

  • physical micro-architecture, i.e., topography of the surfaces (pore size distribution, “roughness”, etc.),
  • chemical properties (surface free energy, enthalpy of adsorption, degree of swelling of surface layers, ion release),
  • micromechanical properties, i.e., surface hardness or flexibility.

These parameters affect processes at the cell-substrate interface cooperatively. The surface is “recognized” by the biological system through chemical and topographic patterns present at the surface, and the viscoelastic properties of the system. However, a detailed and coherent picture of the processes and major mechanisms at the interface is still lacking [1].


Contributions of the participating groups

The group in Mulhouse has shown that a strong deformation of the nucleus of certain cells (osteosarcoma-derived SaOs-2 cells) occurs, when the cells are brought into contact with poly-L-lactic acid (PLLA) films having micropillars with a square morphology on top. The square-pillar dimensions were 7 µm x 7 µm with 4 µm height and 7 µm spacing between the pillars. The adhesion of cells was followed by fluorescent labeling of the nuclei by DAPI and of the actin cytoskeleton by fluorescent phalloidin. Labeling revealed a rather unexpected deformation of the nuclei to an extent which has not been seen before (see figure). A deformation of the actin cytoskeleton was observed along with that. The kinetics of the deformation process confirmed that the changes occur quite rapidly, as soon as the cells start to adhere and spread, i.e., between 6 and 12 hours. c1Surprisingly, the huge nuclear deformation observed did not have any negative influence on the viability, proliferation and differentiation of the cells [2].

The group in Freiburg has strong experience in creating surfaces with tailor-made chemical composition, especially in the context of bio-related applications [3]. Several synthetic methods have been developed for attaching polymers to solid surfaces with high spatial resolution. Such systems have then successfully been used to control the adsorption of proteins to the surfaces which in turn controls strongly the adhesion of biological cells of different types in a spatially controlled way.

The ICS group in Strasbourg has strong expertise in the conception, realization and study of new self-assemblies made from fluorinated amphiphiles [4]. Due to their unique behavior (extreme hydrophobicity and lipophobicity, low surface tension, chemical and biological inertness) perfluoroalkyl compounds provide a tool to induce nanosegregation in thin self-assembled films [4]. Fluorocarbon-hydrocarbon molecular diblocks can be used to control surface chemistry and topography at the nanoscale.


Research project and collaboration

We propose to generate surfaces with tailor-made surface chemisty and well defined micro- and nanotopographies. After preparation of these substrates we want to expose them to biological cells and study their interactions with proteins and cells. A special focus will be placed on how cell organelles, such as the cell nucleus, respond to the nano- and microstructures. We propose to elucidate the influence of surface chemistry at the micro- and nanoscale on protein and cell adhesion and how the cellular organelles respond to surface structuring. It is envisioned to simultaneously control the surface chemistry and topography as well as the mechanical properties of the substrates and to study the response of biological cells onto these properties. One objective of this project will be to understand how cells, and especially cell organelles like the cell nucleus, are able to respond and deform so strongly on a microstructured surface. On the surface side, the cells could seek to minimize the empty space between them and the pillar surface, and thus wet the entire surface in an effort to maximize contact. That could be related to a specific chemistry and protein adsorption capacity of the pillars. The pillar size could also be the reason of this deformation. It appears essential to be able to change the dimensions of microstructures and  also to control the surface chemistry. These possibilities exist in the cleanrooms at the Department of Microsystems Engineering (IMTEK) in Freiburg ,and the group can also capitalize on the experiences of J. Rühe on polymer coatings and of M.-P Krafft on the generation of nanostructures, as outlined above. On the biological side, the cells used in the experiments so far were cancer-derived cells. Their phenotype could explain the deformation observed, since cancer cells are known to deform to a greater extent than most other cell types. The biological mechanisms under this deformation will be studied in Mulhouse by real-time imaging after fluorescent labeling of cytoskeleton and nuclear membrane molecules in presence or not of cytoskeleton inhibitors.


[1]B. Kasemo, J. Gold, Adv. Dent. Res., 1999, 13, 8.
[2]P. Davidson, et al., Adv. Mater., 2009, 21, 3586.
[3]S. Loschonsky, K. Shroff, A. Wörz, O. Prucker, J. Rühe and M. Biesalski, Biomacromolecules, 2008, 9, 543.
[4]M.-P. Krafft and J. G. Riess, Chem. Rev., 2009, 109, 1714.

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