Defined dissipative properties to investigate the role of matrix viscosity on cellular response

本提案的总体目标是生产具有定义耗散特性的材料，以研究基质粘度对细胞响应的作用。原生组织包括细胞和动态的细胞外基质，提供机械和生化线索，负责指导细胞粘附、增殖和分化。机械转导研究中使用的大多数合成材料仅具有确定的弹性特性，提供细胞生长的静态环境。然而，这些材料并不能完全再现细胞在体内的耗散环境（Cantini et al., 2019）。到目前为止，在了解细胞如何对基质粘度做出反应以及如何通过工程设计来影响细胞命运方面，几乎没有取得任何进展。在这个项目中，我们建议制造基于脂质和聚合物的环境，这些环境具有一定范围的粘性和可控的表面迁移率。这些材料平台将用于阐明细胞对基质粘度反应背后的潜在细胞机制。此外，这些材料与肽配体的功能化将用于研究细胞粘附和基质粘度之间对细胞行为的相互作用。这些平台将提高我们对细胞如何粘附和与粘性物质相互作用以及这如何影响细胞行为的理解。从这些系统中获得的知识将被整合到散装水凝胶系统的制造中，该系统将被设计成具有不同的粘性特性、恒定的弹性特性和不同密度的肽配体的功能化。这些水凝胶系统将用于研究二维和三维环境中基质粘度和弹性对细胞行为的相互作用。该项目的结果将提高我们对细胞对基质粘度的反应的理解，为组织工程中使用具有明确弹性和粘性特性的先进材料的工程铺平道路，并为具有生理相关力学特性的体外组织模型的开发铺平道路。cantini， M. et al.（2019）《The Plot Thickens: Matrix Viscosity在细胞力学转导中的新兴作用》，Advanced Healthcare Materials。doi: 10.1002 / adhm.201901259。

The overall aim of this proposal is to produce materials with defined dissipative propertiesto investigate the role of matrix viscosity on cellular response. Native tissues comprisecells and a dynamic extracellular matrix, which provides mechanical and biochemicalcues responsible for guiding cell adhesion, proliferation and differentiation. The majorityof synthetic materials utilised in mechanotransduction research are produced solely withdefined elastic properties, providing a static environment for which cells can grow.However, these materials fail to fully recapitulate the dissipative environment that cellsencounter in vivo (Cantini et al., 2019). Up to this point, little progress has been made inunderstanding how cells respond to matrix viscosity and how this can be engineered toinfluence cell fate. In this project, we propose to fabricate lipid-based and polymer-basedenvironments with defined range of viscous properties and controlled surface mobility.These material platforms will be utilised to elucidate the underlying cellular mechanismsbehind cell response to matrix viscosity. Furthermore, functionalisation of thesematerials with peptide ligands will be utilised to investigate interplay between celladhesion and matrix viscosity on cell behaviour. These platforms will improve ourunderstanding of how cells adhere and interact with viscous materials and how thisinfluences cell behaviour. Knowledge gained from these systems will then beincorporated into the fabrication of bulk hydrogel systems, which will be engineeredwith varying viscous properties, constant elastic properties and functionalised withvarying densities of peptide ligands. These hydrogel systems will be utilised to investigatethe interplay between matrix viscosity and elasticity on cell behaviour in two- and threedimensional environments. The outcomes of this project will improve our understandingof cellular response to matrix viscosity, paving the way for engineering of advancedmaterials with defined elastic and viscous properties for use in tissue engineering anddevelopment of in vitro tissue models with physiologically relevant mechanicalproperties.ReferencesCantini, M. et al. (2019) 'The Plot Thickens: The Emerging Role of Matrix Viscosity in CellMechanotransduction', Advanced Healthcare Materials. doi: 10.1002/adhm.201901259.