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.

该项目的总体目标是开发一个实验系统和一个理论框架的生物启发的活性片，进行控制的形状变化的基础上，自我组织的力量产生的生物聚合物。哺乳动物细胞表面的复合性质，基本上是一个连接到活性肌动球蛋白网络的脂质双层，构成了活性片的一个精致的例子，它是坚固的，可以采取各种几何形状。尽管许多研究工作，肌动球蛋白动力学产生定义的膜形状的基本物理机制仍然知之甚少。这个问题结合了流体脂质膜的流体动力学与活性聚合物网络的力学，其中多个长度尺度上的效应起作用。使用自下而上的方法，我们装饰巨大的单层囊泡（GUV）与薄网络的肌动蛋白丝和肌球蛋白马达和研究网络活动和重组如何驱动膜形状变形在不同的长度尺度。通过将其与尖端的3D晶格光片显微镜（LLSM），定量图像分析和理论相结合，我们希望测试我们的假设，即薄的，产生力的肌动球蛋白凝胶的组成决定了脂质膜如何采用特定的形态（管，椭圆形，哑铃形）。此外，我们计划研究的作用，不对称肌球蛋白分布的GUV变形，通过使用微管辅助蛋白沉积。使用微管抽吸，我们将解决肌动球蛋白修饰的GUV的形状变化的膜张力的作用。在整个项目中，我们将开发和测试这种生物启发的活性片的理论模型。实验和理论工作之间的密切来回沟通将确保有效的实验规划，并将加速整个项目。一个更好的理论和实验掌握肌动球蛋白-脂质膜复合物将在生物物理学，软凝聚物质和工程领域的高度兴趣。该项目将为活性、可控和生物相容性载体的设计提供信息，将揭示细胞形状控制的基本原理，并将加强英国科学界在重组细胞样系统方面的能力。