Research Topics

Engineering Cellular Microenvironments

The local microenvironment of cells is known to exhibit a wealth of regulating cues in affecting cell behaviour. In order to better investigate the in vivo mechanisms of these processes and to maintain an in vivo-like state of in vitro cultivated cells for analytical, biotechnological and therapeutical applications, there is a need to design advanced in vitro cell culture systems. They are designed to allow a tight control of key parameters of the cellular microenvironment. 
In a matrix engineering approach we design and build functional microenvironments for specific in vivo situations, including stem cell niches, cancer progression and wound healing. 

Matrix Reconstitution

Biomolecular engineering of cell scaffolds can be performed through the in vitro reconstitution of supramolecular structures of extracellular matrix components such as proteins, proteoglycans, and glycosaminoglycans. Among the biomacromolecules utilized for that purpose, collagen is distinguished by its abundance in the mammalian organism, its importance for the connective properties of tissues, and a wide variety of specific interactions with nearly 50 different molecules including glycosaminoglycans (e.g. heparin), proteins (e.g. fibronectin), and numerous growth factors. We study the dynamics and structural polymorphism of in vitro reconstituted collagen matrices. Based on a thorough analysis, variations in composition, morphology, mechanics as well as orientational alignment are utilized to design scaffolds in 2D and 3D arrangements.


Selected publications:

  • Biomaterials 52:367 (2015)
  • J Materials Chemistry B 3:8902 (2015)
  • Adv Healthcare Mat 5:1861 (2016)
Short-range cytokine gradients released from microparticles.

Cytokine Presentation

Cytokines and morphogens have been identified as essential cell fate triggers. We engineer in vitro microenvironments for stem cells that allow to control cytokine presentation in both a temporal and spatial fashion. Issues like local gradients as well as the mode of presentation (i.e. bound versus non-bound) are studied in order to build biopolymer matrices with biomimetic characteristics to guide cell behaviour in different physiological situations.

Selected publications:

  • Nat Methods 5:645 (2008)
  • J Control Release 224:59 (2016)
  • Sci Reports 7:5664 (2017)
Hematopoietic stem cell in a matrix-coated microcavity.

in vitro Models of Wound Healing, Cancer Invasion and Stem Cell Niches

Based on our biomimetic models of the extracellular matrix using well-defined, advanced 3D scaffolds based on fibrillar-collagen and biohybrid microstructured polymers we set-up various local microenvironments of early and late stages of dermal wound healing, breast and melanoma cancer cell invasion into the surrounding tissue, and the hematopoietic stem cell niche. We explore important regulating features of these microenvironment in controlling cell behaviour. In this context, we modulate parameters such as the composition, topology, stiffness and interface architecture of the biopolymer matrices, as well as the  presentation of cytokines in bound and soluble manner. Cell fate is studied on population and single cell level using state-of-the-art cell analytical techniques including in situ single cell tracking.

 

Selected publications:

  • Biomater Sci 5:1858 (2017)
  • Adv Healthcare Mat 5:1861 (2016)
  • Sci Reports 6:31951 (2016)

Biosensors

Label free biosensors are standard screening methods in the pharmaceutical industry and in research settings. The advantage of these techniques lies in their ability to probe biomolecular interactions with high selectivity without the risk of altering the affinity of the analyte molecules. The developments in this field are directed towards more affordable sensors with increased throughput and enhanced selectivity and sensitivity. Other sensor devices rely on functional molecular modification and linking technologies where polymeric materials are highly efficient tools as they allow for a broad variety of chemistries and functionalities by easy tunable synthesis strategies. We develop several new sensor principles and modifications including a new force-based detection technique based on soft colloidal probes, nanoparticles and regenerative sensor surfaces.

 

Soft Colloidal Probes

Focus is set on a new label-free screening technique. As detection principle we use soft colloidal probes (SCP) and their adhesion induced mechanical deformation at ligand / receptor interfaces. We are currently adapting the method to construct various biosensors for high-throughput and on-site applications. Further direction is the determination of specific cell material interactions via combination of SCP and AFM. We expect new insight into general concepts of cell adhesion to a ligand functionalized material matrix because the SCP closely mimic the biological context (hydrogels), allow studying cooperative binding under full control of material properties (stiffness, ligand spacing, etc.).

Selected publications: 

  • Langmuir 30:6142 (2014)
  • Phys Chem Chem Phys 17:3014 (2015)
  • Polymer 102:342 (2016)

Signalling at Cell-Material Interfaces

Cell behaviour is strongly regulated by exogenous cues of the local microenvironment. In this context the cellular interaction with natural or synthetic matrices in vivo as well as in vitro causes specific signals, which are transmitted to intracellular signalling cascades regulating in that way complex processes like cell proliferation, differentiation and apoptosis. 
We aim in exploring and dissecting these highly convoluted regulation pathways on biophysical as well as biochemical levels by using combinatorial strategies to design model extracellular microenvironments. Within this approach the characteristics of the materials interfaces based on natural and synthetic biopolymer matrices are modulated like stiffness, topology, binding strength, mobility, orientation or density to build up a molecular and systemic understanding of cell signalling by exogenous materials cues. 

Signalling in Cell Adhesion

We engineer extracellular matrices to explore the adhesive response of cells. The graded control of exogeneous characteristics like matrix stiffness, ligand anchorage, and spatial constraints in a combinatorial manner reveals new insights in the biophysical and biochemical signalling response of cells. The experimental findings are used to develop new descriptions of cell adhesion on a molecular level, as well as in a systems approach.

(Left) Traction stress field of adherent cells. (Right) Stress fibre pattern of laterally constrained cell.

Selected publications:

  • Biophys J 97:2154 (2009)
  • Biophys J 101:1863 (2011)
  • Soft Matter 10:2444 (2014)
Fibronectin fibrils reorganised by an adherent endothelial cell as imaged by confocal laser scanning microscopy.

Matrix Reorganisation

Cells reorganize proteins and glycosaminoglycans in the extracellular space into a complex and highly functional matrix network. In vitro systems are used to actively disturb and modulate the reorganisation processes by exogenous triggers to unravel underlying cellular processes. Structural analysis and dynamic investigations are complemented by biophysical models.

Selected publications:

  • Biophys J 88:527 (2005)
  • Biointerphases 1:93 (2006)
  • Biophys J 101:1863 (2011)
letzte Änderung: 12.09.2017

Kontakt

Prof. Dr. Tilo Pompe
Universität Leipzig
Institute of Biochemistry
Johannisallee 21-23
04103 Leipzig

Telefon: +49 341 97-36931
Telefax: +49 341 97-36939
E-Mail

Sekretariat
Petra Hartmann
Raum 1.34

Telefon: +49 341 97-36930
Telefax: +49 341 97-36939
E-Mail

News

New Paper on Soft Colloidal Probes in Further Biosensor Applications

08.08.2017

A new paper of our group was published in Gels. In a collaborative study with Stephan Schmidt from Düsseldorf we explored new options for the...

New Paper on Myofibroblast Differentiation by Biomimetic Sustained Release of TGF-beta in 3D matrices

01.08.2017

A paper of our group was just published online in Scientific Reports. In the study we demonstrate a low and sustained release TGF-beta1 from...

Our Paper Highlighted on Advanced Science News

06.07.2017

Our recently published paper on macrophage polarization in 3D collagen matrices was highlighted on the Advanced Science News website as one of the...