Nanoparticle-induced lipid membrane deformation influences the design of biomedicine

Abstract

Controlling the physicochemical properties of nanoparticles is important for their performance as drug carriers, pharmaceuticals, or imaging contrast agents in nanomedicine. Predictive models can accelerate experimental designs at reduced time and costs compared to a brute-force approach conventionally used. However, physical principles underlying particle-cell interactions are still poorly understood due to their large size contrast, hindering the model development. In this work, we describe a model that examines the interaction between multiple particles and the membrane of a mammalian cell or an artificial vesicle, thus influencing the outcomes of surface adsorption, detachment or uptake of particles. Compared to existing biophysical models on particle-membrane interactions accounting for membrane adhesion, stretching and bending energies, we make several important updates that are essential to reaching quantitative agreement with existing experimental data. Particle-induced membrane tension changes are crucial to the membrane deformation even at very low surface concentrations (0.1%); we explain this surprising finding using a new length scale previously neglected. Furthermore, a multi-step and non-equilibrium endocytosis mechanism is proposed in the absence of specific receptor-ligand interactions, inspired by recent experimental evidence on the dynamic regulation of membrane tension through the active transport of lipid molecules. We demonstrate the predictive power of our model in generating the adsorption isotherms and shear-induced particle detachment from cell surfaces and the size-dependent rate of particle uptake. Our research provides a framework to design tailor-made nanoparticles with controllable interaction outcomes with various cell types based on a quantitative and fundamental understanding.