Collaborative Proposal: Theoretical, computational, and experimental investigations on the interaction between a lipid bilayer membrane and a solid substrate or particle

该基金支持一个由三名研究人员组成的跨学科团队，使用数学建模，计算机模拟和实验来开发在某些情况下细胞膜行为的改进预测模型。 本研究项目涉及细胞膜和固体颗粒之间相互作用的数学建模，这是一个物理过程，对细胞粘附到固体表面和细胞摄取（内/胞吐）胶体纳米颗粒（例如，药物载体）。 纳米和生物医学工程的进步使得设计智能材料用于更有效的医学治疗成为可能（例如，靶向药物递送）。 这些技术发展是基于理解细胞膜如何与充满离子和大分子的流体环境中的胶体颗粒相互作用。 为了更好地理解复杂流体环境中普遍存在的膜-固体相互作用的物理过程，本项目旨在开发新的数学模型和数值算法，通过考虑随机热波动，电动效应和纳米级现象（例如，分子分层），这在传统的基于连续体的方法中通常被忽略。 微流体实验将平行开发，以指导与具有曲率和/或局部特征的固体表面相互作用的膜的数学和计算建模。 本计画将透过考虑填充于脂双层膜与其他固体表面之间差距的薄液膜的存在，来推进脂双层膜与固体表面及粒子相互作用的数学模拟。 据推测，通过物理上一致的有效相互作用势，基于连续介质的薄膜方程可以捕获LBM在不同离子强度下具有可变润湿性和zeta电位的表面上的宏观铺展动力学。 从数学建模的主要结果之一将是随机非线性润滑方程的LBM和固体表面之间的薄液膜的高度。 理论预测，如LBM粘附力和铺展时间，将与实验结果进行比较，以进行验证和模型改进。 所开发的模型将用于研究LBM（1）在液体中不同离子浓度下的粘附和（2）在具有曲率和局部特征的固体表面上的粘附。

This grant supports an interdisciplinary team of three investigators using mathematical modeling, computer simulations, and experiments to develop improved predictive models for the behavior of cell membranes in certain contexts. This research project concerns the mathematical modeling of the interaction between a cell membrane and a solid particle, a physical process that is essential to cell adhesion to a solid surface and cellular uptake (endo/exocytosis) of colloidal nanoparticles (e.g., drug carriers). Advances in nano- and biomedical engineering have made it possible to design smart materials for more effective medical treatments (e.g., targeted drug delivery). These technical developments are based on understanding how a cell membrane interacts with colloidal particles in a fluid environment filled with ions and macromolecules. It is imperative to better understand the physical processes that underpin such ubiquitous membrane-solid interactions in a complex fluid environment.This project aims to develop new mathematical models and numerical algorithms to describe quantitatively the particle-membrane interactions by considering random thermal fluctuations, electrokinetic effects, and nanoscale phenomena (e.g., molecular layering) that are commonly ignored in conventional continuum-based approaches. Microfluidic experiments will be developed in parallel to guide the mathematical and computational modeling of a membrane interacting with solid surfaces with curvature and/or localized features. This project will advance the mathematical modeling of a lipid bilayer membrane (LBM) interacting with solid surfaces and particles by considering the presence of the thin liquid film filling the gap between the LBM and other solid surfaces. It is hypothesized that, through physically consistent effective interaction potentials, a continuum-based thin film equation can capture the macroscopic spreading dynamics of LBMs on surfaces with variable wetting properties and zeta potentials, under different ionic strengths. One of the main results from the mathematical modeling will be the stochastic nonlinear lubrication equation for the height of the thin liquid film between the LBM and a solid surface. Theoretical predictions, such as LBM adhesion and spreading time, will be compared against experimental results for validation and model refinement. The developed model will be employed to investigate the adhesion of a LBM (1) under different ionic concentrations in the liquid and (2) on solid surfaces with curvature and localized features.