Speaker
Description
The natural extracellular matrix (ECM) is a highly dynamic, supramolecular structure composed of various bioactive molecules held together by specific interactions. The ECM directly interacts with cells and dictates cell behavior to a large extend. Our goal is to synthetically mimic this intricate natural system using supramolecular materials based on hydrogen bonding units. The dynamics of the supramolecular system is shown to be important in the presentation of bioactive epitopes to cells. By design, highly dynamic supramolecular fibrous assemblies decorated with cell adhesive peptide motifs were made and studied in solution. It was shown that these soluble fibrous structures interact with the cell surface, and that the dynamics of bioactive presentation is dependent on the method of supramolecular incorporation. Transient networks and hydrogels composed of similar molecules were shown to have slowed down dynamics, compared to the particles in solution. These hydrogels, when formulated in the right way, were able to enhance cell viability and adhesion. When highly robust solid materials were made using the same supramolecular motif, cell adhesion and migration could be tuned. However, the ECM displays a plethora of bioactive peptide signals. Therefore, a high throughput screening approach was taken using a design of experiments set up, to investigate a synthetic library of peptides supramolecularly incorporated as additives in the base material. It was found that several sequences and/or combinations outperformed others, showing the importance of the high throughput screening approach. Our proposal is that both the dynamics and presentation of bioactive sequences determine cell behavior. In this way we aim to make steps towards the design of a synthetic ECM analogue.
41935605049
