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

生物依赖于巨大的分子复杂性，这使得强大而有效的多功能系统成为可能。通过引入高水平的复杂性，人们越来越努力地设计仿生的、模块化的细胞外基质(ECM)。在工程生物分子系中结合多肽和糖胺聚糖(GAG)提供了一条最相关但只有部分探索的路线。因此，特拉维夫的Ayala Lampel和德累斯顿的Carsten Werner提出的合作项目的总体目标是扩大ECM模拟基质的化学空间，以(I)调节生长因子信号和(Ii)通过使用GAG和肽构建块来控制材料的粘弹性。该工作计划包括设计和合成GAG和肽构建块文库，组合筛选以鉴定新的基质，GAG-肽相互作用的分子水平研究，以及确认所鉴定的基质作为细胞指导生物材料的功能，触发内皮细胞的增殖和形态发生以促进血管生成。这项概述的计划预计将提供一系列具有量身定制的化学成分、结构和可调粘弹性能的新的GAG/肽材料，以及对杂化超分子生物材料中序列-结构关系的新见解。特别是，该方法将提供一种通用的方法来调节基于GAG的3D生物材料的GF活性和粘弹性特性，而不是依赖于自然发生的GAG-GF相互作用。为了实现这一点，该项目将结合Werner实验室设计基于GAG的功能性生物材料的专业知识和Lampel实验室用于多肽设计工具的专业知识。特拉维夫大学(Lampel)和德累斯顿莱布尼茨聚合物研究所/Max Bergmann生物材料中心(Werner)的实验室将通过共享知识和设施以及人员交流，在这一综合方法上进行合作。

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.