Research Area A: Biofunctional Nanostructures and Surfaces – Domain Interfaces of Bio-artificial Hybrid Systems

Small, precise, and versatile: These attributes account for fundamental recent developments of novel building blocks for miniaturized systems, which operate complex process chains in distinct application ranges such as synthesis, product transformation, analytics, and therapeutics. On the nano- and mesoscale, biogenic structures frequently outcompete technically generated materials with respect to diversity, uniformity and inherent activities available. Hence, interest in self-replicating biological particles and scaffolding components has increased substantially worldwide. Several biotemplated devices have manifested superior functionality or even completely novel properties advantageous e.g. for sensor technology or electronic systems. On the other hand, refined diagnostics and manipulation or treatment approaches require improved nanotools and nanofunctionalized synthetic substrates. This is obvious in both medicine and general life sciences, which demand for new methods to interact with organs, cells and subcellular organelles selectively. Therefore, engineering and materials sciences as well as natural and biological disciplines are converging within several branches of research and development these days. Novel areas of investigation are growing, with new collaborative perspectives on existing questions. They often yield unexpectedly valuable data which not only widen the understanding of essential cell biology considerably, but also promote tailor-made solutions for various technological tasks. As a result, the number of international journals focusing on bionanotechnology is increasing remarkably, and the respective scientific conferences attract numerous industrial representatives.

On account of these trends, the network has installed an additional research area which systematically combines well-established nanometric structures of physical, chemical, biological, and technical origin into biohybrid systems of novel functions. Major goal is a balanced availability of complementary structures and methods with sufficient overlap, though, on the research platform, to catalyze synergistic collaborations of which all partners and future engineering and bio-technologies will profit. To ensure international scientific and economic weight, every project works on a distinct unprecedented concept. A common theme is the controlled integration of interacting biological and synthetic components into hybrid systems.

Two projects concentrate on the development of sensorically or analytically active biological units stably working in technical environments, to pave novel ways towards ultrasensitive miniaturized biodetection systems for complex requirements (A3 and A6). Their major targets of high social impact are food, medical and environmental analytes. Starting point of both concepts are viable production routes for suitable biofunctional entities: tailored protein pores apt to be inserted into electrically addressable membrane templates (A3), and plant virus-derived multivalent nucleoprotein scaffolds equipped with distinct enzyme species (A6). Physical, chemical, and bio- as well as gene technological procedures are mutually adapted to generate these nanosized active components. For their insertion into technical devices, a major challenge exists in inventing site-selective placement methods which do not compromise biofunctionality. To this aim, directed externally induced nanometric locomotion, or biophysical self-assembly on biocompatible, selectively addressable nanostructured substrates are exploited. Hence, these elements are of central importance in almost every project within Research Area A. At present, efficient and reliable methods for a targeted insertion of different nanoparticle types into miniaturized chip systems are strongly sought after. The network contributes to this highly topical research area by investigating distinct motive forces. While intermolecular hydrophobic attraction between protein domains and alkane layers is proposed to immobilize biogenic membrane pores in inorganic scaffolds (A3), specific bimolecular recognition events are utilized to guide an entropy-driven self-assembly of nanotubular protein-exposing biological templates (A6). With these projects, the Research Network accommodates two authentic contributions to the rapidly developing field of integrated lab-on-a-chip and nanosensing systems (A3, A6).

While accordingly prepared, advanced technical surfaces are crucial prerequisites for an implantation of biological nanoplayers into micro- and nanodevices, they also interlink the above projects with the medically oriented ones: Here, synthetic interfaces exposing functional nanostructures and molecules interact with complete living cells (A2, A7, A8). Domain borders are thus a second universal theme not only within this Research Area, but also with several other projects in the network (see below). The interplay between cells and technical substrates is most relevant for the progress of tissue or organ replacement and supporting implants. So far frequently neglected aspects discriminating distinct cell types and life stages from each other (A2), and the cells' mechanical responses towards differently nanostructured adhesion areas (A7) are analyzed with newly developed methods including nanoparticulate fluorescent probes. Specifically modified hydrophobic and hydrophilic surfaces, some of them locally fashioned with certain ligands or gold textures (A2, A7), offer many opportunities for effective collaborative work with partner projects within Area A. A single project (A8) even intends to create stably and functionally interconnected living cells and technical components, with the aim to insert nanoscaled spike array electrodes into the cytoplasmic interior of cultured cells and, in the long run, organ tissues: Electricity generated thereby might be a superior source for operating e.g. cardiac pacemakers or insulin pumps.

The diversity of physical, chemical and biological preparation procedures united in the Research Network and namely its Area A demands for profound, reliable quality control, verifying all processing stages with respect to structure, composition, and in some cases activity as well as viability (A2, A7, A8) of the resulting products. Final challenges of all projects are proof-of-concept studies evaluating functionalities of the bio-inorganic hybrid and composite assemblies. At these stages of product characterization, the partners profit most continuously from the well-established cooperation and short distances characteristic of this Research Network in Baden-Wuerttemberg. Every team has access to analytical equipment and expert knowledge of several partners. In the biology sector, molecular, biochemical, and biophysical nucleic acid and protein analytics (namely A3, A6) is complemented by imaging and dynamic techniques, recording several biochemical and cellular parameters (namely A2, A7, A8). Synthetic (organic or inorganic) compounds of the new hybrids undergo characterization via modern, in several cases ultrahigh resolution physical and chemical methods. Advanced microscopy techniques are available for almost any type of material, including composites of soft and hard matter.

The well-balanced configuration facilitates to establish ties with the other research areas. These include, for instance, methods for the generation of nanopatterned layers, topographies and architectures, which can directly benefit from exchange between different teams (e.g. to apply self-organization processes of large molecules and biotemplates in projects A3, A6, B3, D6, and interface preparation technology in A2, A7, A8 and several projects in B). On the other hand, not only qualitative product analysis (e.g. with adapted microscopy techniques and equipment as in C9, D3), but especially in-depth functional analysis of novel building blocks and hybrid devices finds most advantageous facilities on the common research platform (focusing on detection and read-out technology and data evaluation e.g. in A3, A6, B3, C4, D8; on energy production, transport and conversion in A8, B1, and various projects in C). Finally, life science research introduces several advanced analytic methods effective under mild conditions into the network for the first time, which opens up new perspectives for the characterization of complex interactions of inorganic and synthetic nanostructures in the Research Areas B to D.