Hyaluronan in Wound Healing

The Role of Hyaluronan for Keratinocyte Migration

Wound healing is a complex and intricate process tightly regulated by different types of cells. As in many biological processes, hyaluronan (HA) plays an important and multifaceted role in this process^[1]. Following a biophysical approach, we develop well-controlled interfaces to analyze the molecular and mechanical roles of hyaluronan in cellular interactions. Therefore, we chemically modify HA at different positions within the chain. The modified HA is subsequently immobilized on gold-nanostructured interfaces with defined inter-particle distances and additional peptide sequences that promote cell binding via specific integrins. Depending on the inter-particle distance, the interacting HA-receptor might still be able to form clusters. Additionally, cluster formation will also depend on the length of HA molecules and might also be influenced by the immobilization method itself.

These well-controlled HA interfaces are employed to analyze the collective migration (the process of many cells coherently migrating together) of dermal keratinocytes. Additionally these surfaces can be employed to study the wound healing behavior of 3-dimensional organotypic skin models.

[1] Bohaumilitzky et al. Frontiers in Oncology, 2017.

Mechanotransduction in Collective Cell Migration

In the context of collective cell migration the transmission and mediation of cellular tension is of major importance. Tension is transmitted within the multicellular ensemble from cell to cell as well as from cell to substrate. A profound understanding of the generation of cellular forces by this process is essential to understand collective migration processes, which play a fundamental role for example in tissue regeneration, embryogenesis and tumor invasion. For this we are studying the role of geometrical cues for the collective migration of epithelial cells. This work is done in part in collaboration with Prof. U. Schwarz from the University in Heidelberg and financial support is provided by CellNetworks. Further, we study the influence of different substrates on collective cell migration. For that purpose on the one hand we use cRGD, hyaluronic acid and different mimetics (Prof. H. Kessler) to modify our substrate and on the other hand we employ nanostructured surfaces with various distances between the nanoparticles to gain additional control over the surface properties. These experiments are conducted in collaboration with the group of Dr. Lars Hufnagel (EMBL), using the “model wound assay” with micro stencils^[2,3].

 

[2] Das et al. Nature Cell Biology, 2015, 17(3).

[3] Rausch et al. Biointerphases, 2013, 8(1).