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仿生活性片的理论框架，该活性片基于产生力的生物聚合物的自组织而发生受控的形状变化。哺乳动物细胞表面的复合性质，基本上是与活性肌动球蛋白网络相连的脂质双层，构成了活性片的精美例子，该活性片坚固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确定的膜形状的潜在物理机制仍然知之甚少。该问题将流体脂质膜的流体动力学与活性聚合物网络的力学相结合，其中对多个长度尺度的影响发挥着作用。使用自下而上的方法，我们用肌动蛋白丝和肌球蛋白马达的细网络装饰巨型单层囊泡（GUV），并研究网络活动和重组如何驱动不同长度尺度的膜形状变形。通过将其与尖端 3D 点阵光片显微镜 (LLSM)、定量图像分析和理论相结合，我们想要检验我们的假设，即薄的、产生力的肌动球蛋白凝胶的成分决定了脂质膜如何采用特定的形态（管、椭圆体、哑铃） 。此外，我们计划通过使用微量移液器辅助蛋白质沉积来研究不对称肌球蛋白分布对 GUV 变形的作用。使用微量移液器抽吸，我们将解决膜张力对肌动球蛋白修饰的 GUV 形状变化的作用。在整个项目中，我们将开发和测试此类仿生活性片材的理论模型。实验和理论工作之间密切的来回沟通将确保实验的有效规划，并将全面加速项目的进程。更好地理论和实验掌握肌动球蛋白-脂质膜复合材料将在生物物理学、软凝聚态物质和工程领域引起高度关注。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建类细胞系统方面的能力。