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

生命物质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来设计细胞外基质（ECM）的类似生命的模块化模拟物的努力越来越多。将肽和糖胺聚糖（GAG）结合在工程生物分子系综中提供了最相关但仅部分探索的途径之一。因此，Ayala Lampel（特拉维夫）和Carsten Werner（德累斯顿）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）调节生长因子信号传导和（ii）通过使用GAG和肽结构单元原位控制材料的粘弹性。该工作计划包括GAG和肽结构单元库的设计和合成，组合筛选以鉴定新型基质，GAG-肽相互作用的分子水平研究，以及鉴定的基质作为细胞指导性生物材料的功能性的验证，其触发内皮细胞增殖和血管生成的形态发生。概述的计划预计将提供一系列新的GAG/肽材料，具有定制的化学组成，结构和可调的粘弹性，以及对混合超分子生物材料中序列-结构关系的新见解。特别是，该方法将提供一种多功能的手段，用于调节GF活性和粘弹性的3D GAG基生物材料，而不仅仅是那些依赖于天然存在的GAG-GF相互作用。为了实现这一目标，该项目将联合收割机的专业知识的维尔纳实验室的功能性GAG基生物材料的设计与肽设计工具的专业知识的Lampel实验室。特拉维夫大学（Lampel）和德累斯顿莱布尼茨聚合物研究所/马克斯伯格曼生物材料中心（Werner）的实验室将通过共享知识和设施以及交换人员来合作这种综合方法。

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.