Shaping membrane biointerfaces: shape-adaptation in giant vesicles powered by osmotic stresses

塑造膜生物界面：渗透应力驱动的巨型囊泡的形状适应

• 批准号: 1810540
• 负责人: Atul Parikh
• 金额: $ 35万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1810540&HistoricalAwards=false
• 关键词: Shaping; membrane; biointerfaces; shape; adaptation

Nontechnical AbstractChanges in the environment such as freezing or evaporation cause changes in the concentration of salt in the environment of cells and exert stress on the cells. A physical measure of this stress are changes in the osmotic pressure. If left unchecked, changes in the osmotic pressure could cause an instantaneous flow of water out of the cell when the concentration of salt in the cell environment increases and into the cell when the concentration of salt decreases. In the former case the cell shrinks due to dehydration; in the latter case, the cell swells, and may rupture and die. To avoid these catastrophic outcomes, cells have evolved sophisticated mechanisms to regulate their water content in response to changes in the osmotic pressure caused by variations in their local environments. Primitive cells near the dawn of life on Earth on the other hand are likely to have lacked the mechanisms present in today's cells. This proposal makes use of minimal model cells to examine simple mechanisms that could have helped primitive cells to survive changes in osmotic pressure. The proposed research is also providing design rules for synthetic cells capable of responding to chemical stimuli (e.g., osmotic stress) from their environment. A working hypothesis of this effort is that the flexible membrane of the primitive cell responds to osmotic stress by changing its shape and internal organization. The effort integrates fundamental scientific research with (1) education of both undergraduate and graduate students through an interdisciplinary course on physical biology; (2) engagement of underrepresented undergraduate students in STEM research through the Vertically-Integrated-Program at UC Davis; (3) creating opportunities for undergraduate students to participate in collaborative international research at NTU, Singapore, Sorbonne, France; or Chalmers, Sweden; and (4) public dissemination of science through general talks, interviews, and forums surrounding the art and science of living matter. Technical AbstractThe proposed research tests the hypothesis that cell-sized giant vesicles consisting of lipids alone respond to environmental osmotic stress by actively reorganizing the membrane components and undergoing shape remodeling. The investigators seek to obtain a fundamental understanding of how mechanical processes at the soft and flexible membrane interfaces contribute to the balance between stability and adaptability of cells subjected to environmental changes. A long-term expectation is that these efforts will furnish fundamental design principles and experimental capabilities to synthesize active, dynamic, and reconfigurable bio-inspired synthetic compartments and interfaces that display stimuli-responsive behavior and complex, emergent, and life-like functions. The proposed effort seeks to design and construct molecularly tailored giant lipid vesicles that are synthetic cell-sized compartments. These vesicles are subject to controlled osmotic stress, including upshifts and downshifts of the osmotic pressure that take place abruptly or gradually and to uniform or gradient perturbations. The structural adaptability of the vesicles is evaluated by monitoring the molecular redistributions and shape transitions in single vesicles and in ensembles of vesicles primarily using time-resolved fluorescence microscopy. The researchers also seek to create research, educational and outreach opportunities for graduate and undergraduate students that will foster their growth into skilled scientists.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

环境的变化，如冷冻或蒸发，引起细胞环境中盐浓度的变化，并对细胞施加压力。 这种压力的物理测量是渗透压的变化。如果不加以控制，渗透压的变化可能导致水在细胞环境中的盐浓度增加时瞬时流出细胞，并且在盐浓度降低时瞬时流入细胞。在前一种情况下，细胞由于脱水而收缩;在后一种情况下，细胞膨胀，并且可能破裂和死亡。 为了避免这些灾难性的结果，细胞已经进化出复杂的机制来调节其含水量，以响应由局部环境变化引起的渗透压变化。 另一方面，接近地球生命黎明的原始细胞可能缺乏今天细胞中存在的机制。这个提议利用最小的模型细胞来研究可能帮助原始细胞在渗透压变化中生存的简单机制。 拟议的研究还为能够对化学刺激做出反应的合成细胞提供了设计规则（例如，渗透压）。这项工作的一个假设是，原始细胞的柔性膜通过改变其形状和内部组织来响应渗透压。这项工作将基础科学研究与以下方面结合起来：（1）通过物理生物学跨学科课程对本科生和研究生进行教育;（2）通过加州大学戴维斯分校的垂直综合项目，让代表性不足的本科生参与STEM研究;（3）为本科生创造机会，让他们参与NTU、新加坡、法国索邦大学的国际合作研究;或查尔默斯，瑞典;和（4）公众传播科学通过一般会谈，采访，和论坛周围的艺术和科学的生活物质。 技术摘要这项研究验证了这样一个假设，即细胞大小的巨大囊泡仅由脂质组成，通过主动重组膜成分和进行形状重塑来响应环境渗透压。研究人员试图从根本上了解柔软和柔性膜界面的机械过程如何有助于细胞在环境变化中的稳定性和适应性之间的平衡。一个长期的期望是，这些努力将提供基本的设计原则和实验能力，以合成主动的，动态的，可重构的生物启发的合成隔间和界面，显示刺激响应行为和复杂的，紧急的，和生活般的功能。拟议的努力旨在设计和构建分子定制的巨型脂质囊泡，是合成细胞大小的隔间。这些囊泡受到受控的渗透应力，包括突然或逐渐发生的渗透压的升高和降低，以及均匀或梯度的扰动。 的囊泡的结构适应性进行评估，通过监测分子的再分布和形状转变在单个囊泡和囊泡的合奏主要使用时间分辨荧光显微镜。 研究人员还寻求为研究生和本科生创造研究、教育和推广机会，以促进他们成长为熟练的科学家。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Intravesicular Solute Delivery and Surface Area Regulation in Giant Unilamellar Vesicles Driven by Cycles of Osmotic Stresses

• DOI: 10.1021/jacs.3c11679
• 发表时间: 2024-01-24
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Sambre，Pallavi D.;Ho，James C. S.;Parikh，Atul N.
• 通讯作者: Parikh，Atul N.

Nonequilibrium Self-Organization of Lipids into Hierarchically Ordered and Compositionally Graded Cylindrical Smectics

• DOI: 10.1021/acs.langmuir.1c02576
• 发表时间: 2022-01-12
• 期刊: LANGMUIR
• 影响因子: 3.9
• 作者: Ho, James C. S.;Su, Wan-Chih;Liedberg, Bo
• 通讯作者: Liedberg, Bo