Research field B: Controllable nanomaterials

Schematic representation and microscopic image (left open, right closed) of a DNA container
© Seidel (2012)

Coordinator: Jürgen Klingauf, Institute of Medical Physics and Biophysics

Within the research field B functionalization of the materials and structures generated in A are examined regarding their controllablity and responsive behaviour. In natural cells the diversity and complexity of the dynamic processes is mainly based on dynamic non-covalent interactions. Inspired by nature, soft materials shall be generated from non-covalent interacting molecular building blocks, which are capable to react to external stimuli and adopt to changes in the environment. The central objective is to obtain such controllability with regard to well-definded structures and function from non-covalently bound units. Here, comparable with self-assembly, a non-linear behavior of the nanomaterials comes into effect, whereas the direct involvment of theory applying multiscale simulation procedures (ab initio, molecular dynamics, up to coarse-graining and Monte-Carlo models) is of great benefit.

Reference: Seidel 2012

Schematic model of a minimal self-replicating cycle
© A. Dieckmann (2009)

Nikos Doltsinis, Institute of Solid State Theory
Multiscale simulation of self-replicating systems

Rational control of the cell growth: The basic requirement of molecular self-replication - an essential feature of living organisms - is studied be means of synthetic organic self-replicating systems. Therefore, the building blocks of the self-replicators are chosen to be as small as possible to enable an investigation by quantum mechanical calculations and molecular-dynamical simulations. Insights into the rational design of effective replicators are obtained from systematic chemical variation studies.

Relevant preliminary work:

  1. “Elucidating the origin of diastereoselectivity in a self-replicating system: Selfishness vs. altruism.” A. Dieckmann, S. Beniken, C. D. Lorenz, N. L. Doltsinis, G. von Kiedrowski, Chem. Eur. J. 2011, 17, 468-480.
  2. “Unravelling a fulvene based replicator: Experiment and theory in interplay.” A. Dieckmann, S. Beni-ken, C. D. Lorenz, N. L. Doltsinis, G. von Kiedrowski, J. Syst. Chem. 2010, 1, 10.

Reference: A. Dieckmann 2009

Two-dimensional free energy landscape of a cytosine-rich short DNA strand. It is expressed via the first two eigenvectors, resulting from a principal component analysis. Configuration (a) corresponds to the i-motif, (b) and (c) to the hairpin structures and (e) to the fully extended chain.
© WWU / Heuer

Jürgen Klingauf, Institute of Medical Physics and Biophysics

The rational control of the growth of neurons and cells as well as the formation of synaptic contacts on functionalized substrates is a present challenge, which could enable the development of particular cell systems. The results of these experiments deepen the fundamental understanding of synaptic dynamics and plasticity and, in the long term, generate impulses for the development of neuronal interfaces. Chiral surfaces or surfaces modified with proteins and synthetic biocompatible gels control the cell growth for i.a. implants. Within this thematic field, the existing cooperation with the MPI of Molecular Biomedicine and the excellence cluster “Cells in Motion” can be employed. The application of adaptive and responsive materials in the regenerative medicine can be regarded as a long term perspective, whereas it is aimed at a synthetic substitution of the epithelial barrier

Schematic representation of an antibody-modified nanoparticle system for drug targeting application
© Langer, Münster

Klaus Langer, Institute of Pharmaceutical Technology and Biopharmacy
Pharmaceutical technology / Nanostructured dosage forms

The Langer working group is interested in the research field of pharmaceutical / medical nanotechnology, which will be further expanded in the coming years. Nanostructured carrier systems for various drug classes are developed, which actively affect the body distribution of the transported substances in terms of “drug targeting”. As medical application, tumor therapy as well as a diagnostic usage of the systems are in the main focus. For this purpose, on the basis of different starting materials of natural and synthetic origin drug carrier systems are developed, whereas the carrier’s surface properties are optimized regarding a target cell interaction and a prevented accumulation of non-target cells. A particular focus of future work is on the scaling of the preparation methods aiming at preparations, which can be obtained on the pilot-plant scale and thus find access to clinical applications.

Relevant preliminary work:

  1. “Comparative examination of adsorption of serum proteins on HSA- and PLGA-based nanoparticles using SDS-PAGE and LC-MS.” R. Gossmann, E. Fahrländer, M. Hummel, D. Mulac, J. Brockmeyer, K. Langer, Eur. J. Pharm. Biopharm. 2015, 93, 80-87.
  2. “Ligand-modified human serum albumin nanoparticles for targeted gene delivery.” J. Look, N. Wilhelm, H. von Briesen, N. Noske, C. Günther, K. Langer, E. Gorjup, Mol. Pharm. 2015, 12, 3202-3213.
  3. "Nanoparticulate carriers for photodynamic therapy of cholangiocarcinoma: In vitro comparison of various polymer-based nanoparticles.” J. Grünebaum, J. Söbbing, D. Mulac, K. Langer, Int. J. Pharm. 2015, 496, 942-952

Reference: Langer, Münster

Schematic representation of a DNA double helix with metal-mediated base pairs
© J. Müller
The figure shows the network of bacteriochlorophyll a pigments in a monomer of the Fenna-Matthews-Olson complex
© J. Neugebauer

Johannes Neugebauer, Organic Chemistry Institute
Theoretical Methods for Excited States and Photochemistry in Complex Environments

The research of the Neugebauer group focuses on the development of quantum mechanical methods for electronically excited states of complex chemical systems, which are out of reach for conventional electronic structure methods. These include i.a. chromophores in protein complexes, as inclusion compounds, in solution or immobilized on surfaces. These methods are applied to investigate the properties of light-responsive organic materials on increasingly realistic models. In terms of method development, the group aims at providing efficient quantum chemical methods for photochemical investigations in (bio-)macromolecules. These can be used to investigate photochemical reaction pathways and thus, contributing to a better understanding of the light control mechanism of DNA or protein binding on vesicles.

Relevant preliminary work:

  1. “Including Protein Density Relaxation Effects in First-Principles Embedding Calculations of Cofactor Excitation Energies.” A. Goez, J. Neugebauer, Mol. Phys. 2016, in press, DOI: 10.1080/00268976.2016.1199823.
  2. “Analytical Gradients for Excitation Energies from Frozen-Density Embedding.” A. Kovyrshin, J. Neugebauer, Phys. Chem. Chem. Phys. 2016, 18, 20955-20975.
  3. “State-Specific Embedding Potentials for Excitation-Energy Calculations.” C. Daday, C. König, O. Valsson, J. Neugebauer, C. Filippi, , J. Chem. Theory Comput. 2013, 9, 2355-2367

Reference: 1.

Schematic representation of the light induced formation and dissolution of ternary vesicle complexes consisting of cyclodextrins, azobenzene spermine conjugates and DNA. The accumulation of target-specific ligands with light-responsive conjugates at the vesicle surface could yield a diverse transportation system for binding and releasing DNA, RNA and thus being applicable for gene therapy

Bart Jan Ravoo, Organic Chemistry Institute
Synthetic vesicles

The general objective of our research is applying molecules as building blocks for the construction of soft materials and nanoscale structures by means of self-assembly. The formation of complex and dynamic superstructures based on various small molecules results in chemical systems featuring new properties that go beyond the actual sum of the single components. Our group works on two main topics: Biomimetic supramolecular chemistry and surface modifications via molecular self-assembly.
In the field of biomimetic supramolecular chemistry we investigate the self-assembly of molecules and colloids in aqueous solution. We employ non-covalent interactions to generate larger structures from molecular building blocks. Multiple weak interactions result in a strong and selective multivalent interaction. One main research topic involves receptor molecules incorporated vesicles, such as cyclodextrins. The multivalent recognition of guest molecules on the vesicle surface, and the according interaction among the vesicles, serve as biomimetic model system for the biological cell-cell recognition and innovative container for drugs. A further research topic is based in the development of synthetic carbohydrate receptors. Applying a dynamic-combinatorial approach oligomers and macrocyclic carbohydrate receptors are formed from peptidic building blocks. These receptors are capable to effectively and selectively bind carbohydrates both in water and on membrane surfaces. In the area of surface modifications by self-assembly, we investigate the preparation and the resulting properties of molecular monolayers on solid substrates. We combine bottom-up self-assembly with top-down lithography, for example to structure surfaces by microcontact printing with reactive molecular inks. Microcontact printing is applied to prepare chemical and biological surface templates including protein, nucleotide and carbohydrate based chips. In the long-term we aim at the synthesis of adaptive surfaces.

Reference: “Light-Responsive Capture and Release of DNA in a Ternary Supramolecular Complex.” S. K. M. Nalluri, J. Voskuhl, J. B. Bultema, E. J. Boekema, B. J. Ravoo, Angew. Chem. Int. Ed. 2011, 50, 9747-9751; Angew. Chem. 2011, 123, 9921-9925.

Cell moving to an inflammatory stimulus. Cytoskeletal proteins polarize during migration (actin red, tubulin green, nucleus blue)
© Marc Wolf, Johannes Roth, WWU Münster

Johannes Roth, Institute of Immunology:
Target-orientated immunomodulation of specific leucocyte populations by immune functional nanoparticles

The treatment of chronic inflammatory diseases, such as rheumatoid arthritis, allergies, autoimmune diseases or inflammatory bowel diseases, is still challenging due to serious side effects. It is becoming increasingly clear, that specific subpopulations of leucocytes play a significant role for diverse functions in the beginning but also in the termination of inflammatory reactions. Developing new immunosuppressive pharmaceuticals usually takes decades. Alternatively, a precise addressability of defined leucocyte populations via specific molecular target structures even applying common drugs would allow a more effective treatment with less side effects. Our working group provides a high expertise to identify clinically relevant target structures on defined leucocyte populations. In cooperation with research partners of the SoN and using different nanoparticle based technologies new methods are established, which allow a selective application of substances for therapeutic or diagnostic purposes in molecular defined leukocytes. In this context, our expertise can be utilized to verify the biocompatibility of newly developed, bioactive nanoparticles in leucocytes in vitro, and the efficiency of numerous, clinically relevant inflammatory animal models in vivo.

Relevant preliminary work:

  1. ”MRP8 and MRP14 are novel endogenous activators of toll-like receptor 4 promoting lethal endotoxin-induced shock.” T. Vogl, K. Tenbrock, S. Ludwig, N. Leukert, C. Ehrhardt, M. A. D. van Zoelen, W. Nacken, D. Foell, T. van der Poll, C. Sorg, J. Roth, Nat. Med. 2007, 13, 1042-1049.
  2. “Glucocorticoids promote survival of anti-inflammatory macrophages via stimulation of adenosine receptor A3.” K. Barczyk, J. M. Ehrchen, K. Tenbrock, M. Ahlmann, J. Kneidl, D. Viemann, J. Roth, Blood 2010, 116, 446-455.
  3. “Alarmin S100A8/S100A9 as a biomarker of local inflammatory activity.” T. Vogl, M. Eisenblätter, T. Völler, S. Zenker, S. Hermann, P. van Lent, A. Faust, C. Geyer, B. Petersen, K. Roebrock, M. Schäfers, C. Bremer, J. Roth, Nat. Commun. 2014, 5, 4593.

Reference: Wolf, Johannes Roth, Institute of Immunology, WWU Münster

Secondary electron microscopic image of freeze-dried hollow polyelectrolyte capsules.
© M. Schöndorf

Monika Schönhoff, Institute of Physical Chemistry:
Nanocontainer for drug encapsulation

Smallest particles with sizes around 100 nm are capable to penetrate into cells and to selectively transport drugs. Exemplarily, in the inside of polymeric hollow capsules composed of polyions a diversity of small molecules can be encapsulated. Fundamental investigations regarding the incorporation, dynamics and transportation of such guest molecules using dynamic NMR methods are performed. Applying a method, which was particularly promoted from the Schönhoff group, and based on diffusion experiments, the localization of the probe molecules inside the particle, as well as the permeation through the capsule wall is determined. Both drug molecules and appropriate model substances, which are relevant with regard to the development of colloidal carrier systems, are studied. Furthermore, switchable particles are developed featuring a controlled release upon external trigger, such as temperature or pH.

Relevant preliminary work:

  1. “Polyelectrolyte multilayer capsules: Nanostructure and visualisation of nanopores in the wall.” V. Krzyzanek, N. Sporenberg, U. Keller, J. Guddorf, R. Reichelt, M. Schönhoff, Soft Matter 2011, 7, 7034- 7041.
  2. “pH-triggered Polyelectrolyte Release from Surface Modified Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles.” M. Häuser, K. Langer, M. Schönhoff, Beilstein J. Nanotechnol. 2015, 6, 2504-2512.

Reference: 1.

Representation of the yeast plasma membrane with different domains indicated in color. Left and center are artistic illustrations of domains, right shows two network forming domains for proteins labeled with RFP and GFP, respectively
© R. Wedlich-Söldner