CAREER: Domain boundary phenomena and composition fluctuations in heterogeneous lipid membrane mixtures

职业：异质脂膜混合物中的域边界现象和成分波动

• 批准号: 1053857
• 负责人: Tobias Baumgart
• 金额: $ 32.8万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1053857&HistoricalAwards=false
• 关键词: CAREER; Domain; boundary; phenomena; composition

CBET-1053857Baumgart, TobiasCell membranes contain regions where specific lipids and proteins become concentrated. Locally concentrating functional molecules enhances intermolecular interactions and is a mechanism widely used in biological systems. Compositional domains (often called rafts) play important roles in membrane function, including signaling and trafficking. The principles behind membrane domain formation and properties of the particularly important boundaries of such domains are currently not well understood. Membranes self-assembled from lipid mixtures can be used as experimental models that capture many features of biological membranes. In this project, the PI will elucidate the physicochemical properties and control parameters that affect domain boundaries, as well as the dynamics of mixing/demixing transitions and composition fluctuations in multi-component membranes. Intellectual Merit The study of interfacial tension (or surface tension) between three-dimensional fluid phases has been an extremely active research area. Tension at the phase boundary of two-dimensional fluid phase domains (line tension) in lipid membranes, however, is largely unexplored. Line tension is assumed to regulate domain size, morphology, and lifetime, and thus is a critically important parameter of heterogeneous membranes. The PI will identify biologically relevant equivalents of surfactants in two-dimensional fluids. Such linactants may modulate line tension and could trigger in-plane emulsification transitions which have been hypothesized to be involved in biomembrane function, but which have not yet been experimentally demonstrated. Several biomolecules have been hypothesized to function as linactants. Line tension measurements are required to test these assumptions and to identify new biologically relevant linactants. The PI will elucidate molecular determinants of linactancy that will help in the design of new linactants. Line tension models have recently been developed that provide a framework for understanding linactancy. Experimental data are now required to test these models. With these, the PI will test specific aspects of current line tension theories and collaborate with theoreticians in the development of new models. The dynamics of mixing transitions and local composition fluctuations in membranes are largely unexplored. To study these aspects, the PI will use optical imaging methods that can provide information not obtainable by classical scattering techniques. The experimental analysis of these phenomena will enable the PI to test existing theories. This research will help understand how biomembrane function couples with in-plane membrane structure. Broader Impacts Understanding and the ability to control the formation and properties of membrane domains ares important for elucidating normal cell membrane function and its perturbation in pathological situations. The enrichment of molecules along membrane phase boundaries may prove to be a mechanism widely employed in biomembranes to regulate functional molecular interactions. The fabrication of biomolecule patterns on surfaces that mimic biomembranes furthermore holds great potential for the design of materials and devices that can be used for biosensing, molecular diagnostics, drug screening, and information storage. However, a problem that occurs in the development of smaller and smaller pattern features is that domain boundary energy (line tension) leads to degradation of nanoscale patterns. The PI will identify, develop, and characterize linactants that may function as domain boundary stabilizers for use in these bioengineering applications. Research on phenomena associated with the mixing behavior of two-dimensional fluids, and its interpretation by means of thermodynamic, statistical mechanical and hydrodynamic models, present opportunities for the integration of research and teaching. The PI has newly developed a two-day workshop for high school teachers. This workshop, co-directed with an outstanding high school teacher, identifies common misconceptions and knowledge gaps in thermochemistry and thermodynamics.

CBET-1053857 Baumgart，Tobias细胞膜包含特定脂类和蛋白质集中的区域。局部浓缩功能分子增强了分子间的相互作用，是生物系统中广泛使用的一种机制。组成结构域(通常称为筏子)在膜功能中发挥着重要作用，包括信号和运输。膜结构域形成背后的原理和这种结构域特别重要的边界的性质目前还不是很清楚。从脂质混合物中自组装的膜可以用作实验模型，捕捉到生物膜的许多特征。在这个项目中，PI将阐明影响结构域边界的物理化学性质和控制参数，以及多组分膜中混合/分离转变和组成波动的动力学。关于三维流体相间界面张力(或表面张力)的研究一直是一个非常活跃的研究领域。然而，脂膜中二维流体相区相边界的张力(线张力)在很大程度上是未知的。线张力被认为是调节结构域大小、形态和寿命的重要参数，因此是非均相膜的重要参数。PI将识别二维流体中表面活性剂的生物相关等价物。这类乳化剂可以调节线张力，并可以触发平面内乳化转变，这些转变被认为与生物膜功能有关，但尚未得到实验证明。已有几种生物分子被假设为起链状作用。需要线张力测量来检验这些假设，并确定新的生物相关的线状物质。PI将阐明线性的分子决定因素，这将有助于设计新的交联剂。最近开发的线张力模型为理解线性提供了一个框架。现在需要实验数据来测试这些模型。有了这些，PI将测试当前线张力理论的特定方面，并与理论家合作开发新模型。膜中混合转变和局部组成波动的动力学在很大程度上是未知的。为了研究这些方面，PI将使用光学成像方法，这些方法可以提供经典散射技术无法获得的信息。对这些现象的实验分析将使PI能够检验现有的理论。这项研究将有助于理解生物膜如何与平面内膜结构相耦合。更广泛的影响，理解和控制膜域的形成和性质的能力对于阐明正常的细胞膜功能及其在病理情况下的扰动是重要的。分子沿膜相边界的浓缩可能被证明是生物膜中广泛使用的一种调节功能分子相互作用的机制。此外，在表面模拟生物膜的生物分子图案的制造在设计可用于生物传感、分子诊断、药物筛选和信息存储的材料和器件方面具有巨大的潜力。然而，在开发越来越小的图案特征时出现的一个问题是，域边界能量(线张力)导致纳米级图案的退化。PI将识别、开发和表征可在这些生物工程应用中用作结构域边界稳定剂的链接剂。研究与二维流体混合行为有关的现象，并用热力学、统计力学和流体力学模型对其进行解释，为研究和教学的结合提供了机会。PI最近为高中教师开发了一个为期两天的研讨会。这个工作坊与一位杰出的高中老师共同指导，确定了热力学和化学中常见的误解和知识差距。