Expanding the matrix space – modulating growth factor signals by cell instructive GAG-peptide hydrogels with customizable viscoelastic properties

• Applicant: Professor Dr. Carsten Werner
• Subject Area: Biomaterials
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 455424195

Living matter relies on a tremendous molecular complexity that enables robust and effective multifunctional systems. There are increasing efforts to design life-like, modular mimics of the extracellular matrix (ECM) by introducing high levels of complexity. Combining peptides and glycosaminoglycans (GAG) in engineered biomolecular ensembles offers one of the most relevant yet only partially explored routes. Accordingly, the overarching goal of proposed collaborative project of Ayala Lampel (Tel Aviv) and Carsten Werner (Dresden) is to expand the chemical space of ECM-mimetic matrices to (i) modulate growth factor signaling and (ii) control the viscoelastic properties of the materials in situ by using GAG and peptide building blocks. The work program includes the design and synthesis of libraries of GAG and peptide building blocks, combinatorial screening to identify novel matrices, molecular level studies of GAG-peptide interactions, and the validation of the identified matrices’ functionality as cell-instructive biomaterials triggering proliferation and morphogenesis of endothelial cells towards angiogenesis. The outlined program is expected to deliver a range of new GAG/peptide materials with tailored chemical composition, structures, and tunable viscoelastic properties as well as new insights into the sequence-structure relationship in hybrid supramolecular biomaterials. In particular, the approach will provide a versatile means for modulating GF activity and viscoelastic properties of 3D GAG-based biomaterials beyond those relying on naturally occurring GAG-GF interactions.To achieve this, the project will combine the expertise of the Werner lab for the design of functional GAG-based biomaterials with the expertise of the Lampel lab for peptide design tools. The laboratories at the Tel Aviv University (Lampel) and Leibniz Institute of Polymer Research Dresden/Max Bergmann Center of Biomaterials (Werner) will cooperate on this integrative approach by sharing knowledge and facilities, and exchanging personnel.

• DFG Programme: Research Grants
• International Connection: Israel
• International Co-Applicant: Dr. Ayala Lampel