Nanobiotechnology

Our goal is to investigate and control complex processes in biological systems by using physical and chemical methods. Very often we make use of nanomaterials as building blocks to engineer functional nanoscaled devices. These devices are able to collect information or trigger processes in biological systems and finally biological functions. Below you can find some examples of recently published work.

We thank for generous funding from the DFG, FCI, EXC 171, CNMPB, VW Stiftung, MWK Lower Saxony, life@nano.

1. New materials, surface chemistry and photophysics


Nanomaterials are versatile building blocks for nanoscale sensors and actuators because they share the same length scale as many biological structures. Additionally, the low-dimensionality and quantum-confinement very often results in interesting and unique physical and chemical properties. We study optoelectronic properties of materials to understand fundamental mechanisms and to identify materials that provide properties for completely new applications.
Among the different nanomaterials carbon nanomaterials have many extremely useful characteristics and provide rich structural, optical and chemical diversity. For example, carbon nanotubes are hollow cylinders of one-atom-thick sheets of carbon. All these properties and their size make carbon nanotubes ideal materials for different types of biomedical applications (Advanced Drug Delivery Reviews 2013, Analytical and Bioanalytical Chemistry 2016). One of our goals is to understand the photophysics of carbon nanotubes and to use them for biosensing (JPC 2016).



Figure 1: Basic concept of carbon nanotube-based fluorescent sensors/probes and single nano sensor response to dopamine.

2. Near Infrared spectroscopy and microscopy


The near infrared (nIR) is a special region of the electromagnetic spectrum. Humans cannot see it and it falls into the tissue-transparency window because nIR light can penetrate deeper into tissue. We use and develop near infrared spectroscopy to study new materials. For example, carbon nantotubes display fluorescence in the nIR and nIR spectroscopy and microscopy is useful to study basic mechanism such as the structure of biomolecules on their surface (JPC 2016, JACS 2014, PNAS 2017).

3. Chemical imaging and biosensors


Chemical imaging is a powerful concept. It provides spatiotemporal information about sample. A typical example is Raman spectroscopy-based imaging. We develop fluorescent nanosensors and use many of them to image molecules with high spatiotemporal resolution. At present, direct optical detection of neurotransmitter changes around neurons is an unsolved issue. Therefore many aspects of chemical neurotransmission remain unexplored, which hampers understanding the brain. We have recently developed the first carbon nanotube-based fluorescent sensor of dopamine in the near infrared (JACS 2014) and used it to image dopamine release from cells (PNAS 2017). A key challenge to create fast, selective and sensitive nanosensors is controlling the organic phase around the nanomaterial (Nature Nano 2013, JPC 2016).



Figure 2: Imaging neurotransmitter release with fluorescent nanosensors. From PNAS 2017.

The organic corona determines how an analyte interacts with e.g. the carbon nanotube and how it affects the optoelectronic properties. This topic is directly related to understanding in general how molecules interact with the organic (corona) phase around nanoparticles and influence their optoelectronic properties. Our long-term goal is to use these and other label-free optical sensors to map neurotransmitter release events in neural circuits and immunological systems and gain fundamental new insights into chemical communication between cells.



Figure 3: Monte-Carlo simulations of fluorescent sensors reveal resolution limits and provide mechanistic insights. From ACS Nano 2017.

We furthermore use theoretical methods to explore the resolution limits of imaging with nanosensors (see figure 3). Such simulations help us to understand how a perfect sensor should be designed and which biological processes are resolvable (ACS Nano 2017).

4.Cell Biophysics


Our work in this space is motivated by the complex interactions between white blood cells (neutrophils) and other surfaces e.g. blood aggregates (thrombi) in the blood stream. This process is important because it determines inflammatory processes and tissue damage after a stroke or heart attack.



Figure 4: Biofunctionalization approach to mimic the surface of a blood platelet and adhesion maturation of neutrophils. From Kruss et al. ACS Nano 2013.


Neutrophils interact with thrombi via the integrin Mac-1 and the platelet receptor glycoprotein Ibalpha (GPIbalpha), which plays an important role in blood coagulation. I quantitatively determined the conditions for neutrophil adhesion in a biomimetic system, which allowed precise adjustment of the spacings between GPIbalpha on the nanoscale. Our results show that the number of single receptor/ligand bonds between Mac-1 and GPIbalpha determine if a cell can attach on a surface under flow. In contrast, if the cell has attached to the surface, adhesion kinetics depend only slightly on the number of ligands. In the future, this system will be useful to determine optimum therapeutic ranges for targeting this interaction (see ACS Nano 2014, ACS Nano 2013, Lab on a Chip 2012).
Cell adhesion on artificial surfaces also determines the biocompatibility of medical implants. We established nanostructuring and biofunctionalization techniques that improve the biocompatibility of medically relevant synthetic materials (e.g. vascular grafts). To this end, we developed a method for the transfer of nanoparticles to polymers such as Teflon or hydrogels in order to functionalize them and increase the adhesion of 'wanted' cells. Additionally, we developed a process to grow gold-silver hybrid nanoparticle patterns on polymers, which is highly relevant for antimicrobial coatings of implants (Adv. Mat. 2010, Langmuir 2012).