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

CBET-1053857 Baumgart，Tobias细胞膜含有特定脂质和蛋白质浓缩的区域。局部聚集功能分子增强分子间相互作用，是生物系统中广泛使用的机制。组成域（通常称为筏）在膜功能中发挥重要作用，包括信号传导和运输。膜结构域形成背后的原理和这些结构域的特别重要的边界的性质目前还没有很好地理解。由脂质混合物自组装的膜可以用作捕获生物膜的许多特征的实验模型。在这个项目中，PI将阐明影响域边界的物理化学性质和控制参数，以及多组分膜中混合/分层过渡和成分波动的动力学。三维流体相之间的界面张力（或表面张力）的研究一直是一个非常活跃的研究领域。然而，在脂质膜中的二维流体相域（线张力）的相边界处的张力在很大程度上是未探索的。线张力被认为可以调节结构域的尺寸、形态和寿命，因此是非均质膜的一个至关重要的参数。PI将确定二维流体中表面活性剂的生物相关等效物。这样的linactants可以调节线张力，并可能触发面内乳化转变，这已被假设为涉及生物膜功能，但尚未得到实验证明。几种生物分子已被假设为作为linactants的功能。线张力测量需要测试这些假设，并确定新的生物相关的linactants。PI将阐明分子决定因素的linactancy，这将有助于设计新的linactants。线张力模型最近已经开发，提供了一个框架，了解linactancy。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成分波动的动态特性在很大程度上尚未探索。为了研究这些方面，PI将使用光学成像方法，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能够测试现有的理论。这项研究将有助于了解生物膜功能如何与平面膜结构耦合。更广泛的影响理解和控制膜结构域的形成和性质的能力对于阐明正常细胞膜功能及其在病理情况下的扰动战神重要的。分子沿着膜相界富集可能被证明是生物膜中广泛采用的调节功能分子相互作用的机制。此外，在模拟生物膜的表面上制造生物分子图案对于可用于生物传感、分子诊断、药物筛选和信息存储的材料和装置的设计具有巨大潜力。然而，在越来越小的图案特征的开发中出现的一个问题是，畴界能量（线张力）导致纳米级图案的退化。PI将识别，开发和表征可能作为域边界稳定剂用于这些生物工程应用的linactants。研究与二维流体的混合行为相关的现象，并通过热力学，统计力学和流体动力学模型对其进行解释，为研究和教学的整合提供了机会。PI最近为高中教师开发了一个为期两天的讲习班。这个研讨会，与一位优秀的高中教师共同指导，确定了热化学和热力学中常见的误解和知识差距。

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.