Bio-inspired active sheets: control of membrane shape dynamics by force-generating biopolymer networks

仿生活性片：通过产生力的生物聚合物网络控制膜形状动力学

• 批准号: EP/V043498/1
• 负责人: Darius Koester
• 金额: $ 76.08万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FV043498%2F1
• 关键词: Bio; inspired; active; sheets; control

The overall aim of this project is to develop an experimental system and a theoretical framework of bio-inspired active sheets that undergo controlled shape changes based on self-organisation of force generating biopolymers. The composite nature of the surface of mammalian cells, basically a lipid bilayer linked to an active actomyosin network, constitutes an exquisite example of an active sheet, that is robust and can take various geometries. Despite many research efforts, the underlying physical mechanisms by which actomyosin dynamics generate defined membrane shapes remain poorly understood. This problem combines hydrodynamics of the fluid lipid membrane with the mechanics of active polymer networks where effects on multiple length scales play a role. Using a bottom-up approach we decorate giant unilamellar vesicles (GUVs) with thin networks of actin filaments and myosin motors and study how network activity and reorganisation drives membrane shape deformations at different length scales. By combining this with cutting edge 3D lattice light sheet microscopy (LLSM), quantitative image analysis and theory we want to test our hypothesis that the composition of thin, force generating actomyosin gels determines how lipid membranes adopt specific morphologies (tubes, ellipsoid, dumbbell). In addition, we plan to study the role of asymmetrical myosin distribution on GUV deformations by using micropipette assisted protein deposition. Using micropipette aspiration, we will address the role of membrane tension on shape changes in actomyosin decorated GUVs. Throughout the project, we will develop and test a theoretical model of such bio-inspired active sheets. The close back and forth communication between experimental and theoretical work will ensure an efficient planning of experiments and will accelerate the project overall. A better theoretical and experimental grasp of the actomyosin-lipid membrane composite will be of high interest in the fields of biophysics, soft condensed matter, and engineering. This project will inform the design of active, controllable, and biocompatible carriers, will uncover basic principles governing cell shape control and will strengthen the capabilities of the UK science community in reconstituted, cell-like systems.

该项目的总体目的是开发一个实验系统和一个由生物启发的活性纸的理论框架，该材料基于生成生物聚合物的自我组织而受到控制形状的变化。哺乳动物细胞表面的复合性质，基本上是一种与活性肌球蛋白网络相关的脂质双层，构成了活性片的精美例子，它是强大的，并且可以采用各种几何形状。尽管进行了许多研究工作，但肌动球蛋白动力学产生定义的膜形状的潜在物理机制仍然知之甚少。这个问题将流体脂质膜的流体动力与活性聚合物网络的力学结合在一起，其中对多个长度尺度的影响起作用。使用自下而上的方法，我们用肌动蛋白丝和肌球蛋白电机的薄网络装饰巨型单层囊泡（GUV），并研究网络活动和重组如何在不同长度尺度上驱动膜形状变形。通过将其与尖端3D晶格光片显微镜（LLSM）相结合，定量图像分析和理论我们希望测试我们的假设，即薄的，产生肌动蛋白凝胶的组成决定了脂质膜如何采用特定的形态（管，Ellipsoid，Dumbbell）。此外，我们计划通过使用微孔辅助蛋白沉积来研究不对称肌球蛋白分布在GUV变形上的作用。使用MicroPipette抽吸，我们将解决膜张力在肌动球蛋白装饰的GUV中的形状变化中的作用。在整个项目中，我们将开发和测试这种生物启发的活动表的理论模型。实验和理论工作之间的来回沟通将确保实验的有效计划，并将整体加速项目。对肌动蛋白脂质膜复合材料的理论和实验掌握更好，将在生物物理学，软凝结物质和工程领域中引起人们的兴趣。该项目将为主动，可控制和生物相容性的载体的设计提供信息，将揭示有关细胞形状控制的基本原则，并将增强英国科学界在重建的类似细胞的系统中的能力。