弹性流体生物膜包覆纳米材料的力学行为研究

Phagocytosis is a fundamental cellular process by which specific immune cells such as neutrophils and macrophages bind and engulf large solid particles through membrane wrapping, and degrade them eventually. The key steps of the phagocytosis involves remodeling and protrusion of the actin cytoskeleton underneath the cell membrane, membrane spreading over the engulfed particle, variation of the cell volume and area as well as large and complex deformation of the cell. Although phagocytosis is of vital importance to the immune system, its mechanics and mechanism of engulfment remains poorly understood. So far large amounts of experimental studies have been carried out and indicate that the membrane wrapping in phagocytosis significantly depends on the size, shape, surface properties, and elasticity of the particles. However, there are relatively few but limited theoretical models on the engulfment of cells due to its high degree of complexity. In this project we will propose theoretical modeling and conduct computational simulations to comprehensively and systematically investigate and understand how phagocytosis depends on the particle properties mentioned above. The proposed interdisciplinary work incorporating input from mechanics, physics, biology and nanotechnology will generate new knowledge and fundamental understanding in cell mechanics that may provide useful insights and guidelines for a broad range of implications in nano and bio-technologies as well as controlled therapeutics.

吞噬作用是生物体最基本的防卫机制之一。细胞在吞噬过程中采用细胞膜主动包覆吞入物的方式将外界物质输送到细胞内部。对细胞膜包覆力学行为的研究有助于更深地理解吞噬细胞的生命活动，研发出对环境和人体健康更安全的纳米材料和更有效的药物载体。尽管人们针对吞噬过程做了大量实验观测，但却缺乏对细胞膜包覆这一关键力学行为的定量描述，也未有准确和完善的力学模型被提出，人们对影响膜包覆行为的力学因素及其重要性也不清楚。本项目从力学角度出发，结合理论建模和计算模拟，深入系统地研究吞噬过程中的细胞膜包覆吞入物的力学行为；确定影响膜包覆行为的力学参量及其随吞噬过程变化的规律；考察吞入物尺寸、表面亲和度、形状、弹性性能对膜包覆行为的影响，寻找调控吞噬作用的主要因素。研究成果将帮助人们了解什么样的吞入物对环境和人体健康是安全的，以及如何设计作为药物载体的吞入物使其能躲避或易于逃离吞噬作用，并为其他胞吞作用的研究提供借鉴。

纳米材料与生物膜的力学相互作用对很多细胞活动起到至关重要的作用，例如细胞吞噬、细胞间或细胞内的物质输运、膜变形调控的生物功能。本项目围绕生物膜壳结构与纳米材料的力学相互作用，结合理论建模、实验和分子动力学模拟，系统考察了相互作用的弹性效应、几何维度效应、生物膜非线性大变形等方面，在纳米颗粒与脂滴的受限力学行为、囊泡与生物膜的非线性形变与力学响应以及生物膜管形成、形变与分叉演化力学方面取得了重要科学发现和原创性成果。项目成果发表SCI论文16篇。项目负责人在项目执行期间获得国家优秀青年基金项目，一位博士后研究人员出站入职中科院力学研究所，两名博士研究生毕业，一名硕士研究生毕业。