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

定义耗散特性以研究基质粘度对细胞反应的作用

• 批准号: 2441947
• 金额: --
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2441947
• 关键词: Defined; dissipative; properties; investigate; role

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.

该提案的总体目标是生产具有确定耗散特性的材料，以研究基质粘度对细胞反应的作用。天然组织包含细胞和动态的细胞外基质，其提供负责引导细胞粘附、增殖和分化的机械和生物化学信号。在机械力传导研究中使用的大多数合成材料仅具有限定的弹性性质，提供细胞可以生长的静态环境。然而，这些材料不能完全再现细胞在体内遇到的耗散环境（Cantini等人，2019年）。到目前为止，在理解细胞如何对基质粘度做出反应以及如何通过工程改造来影响细胞命运方面几乎没有取得进展。在这个项目中，我们建议制造基于脂质和聚合物的环境，具有确定的粘性特性和可控的表面流动性。这些材料平台将用于阐明细胞对基质粘度响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材料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纳入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，并用不同密度的肽配体进行功能化。这些水凝胶系统将被用来investigatethe基质粘度和弹性之间的相互作用对细胞行为在二维和三维环境。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，为具有确定的弹性和粘性特性的先进材料的工程化铺平道路，用于组织工程和具有生理相关机械特性的体外组织模型的开发。（2019）“情节增厚：基质粘度在细胞机械转导中的新兴作用”，Advanced Healthcare Materials。doi：10.1002/adhm.201901259。