Advancements in Engineering Planar Model Cell Membranes: Current Techniques, Applications, and Future Perspectives

Abstract

Cell membranes are crucial elements in living organisms, serving as protective barriers and providing structural support for cells. They regulate numerous exchange and communication processes between cells and their environment, including interactions with other cells, tissues, ions, xenobiotics, and drugs. However, the complexity and heterogeneity of cell membranes-comprising two asymmetric layers with varying compositions across different cell types and states (e.g., healthy vs. diseased)-along with the challenges of manipulating real cell membranes represent significant obstacles for in vivo studies. To address these challenges, researchers have developed various methodologies to create model cell membranes or membrane fragments, including mono- or bilayers organized in planar systems. These models facilitate fundamental studies on membrane component interactions as well as the interactions of membrane components with external agents, such as drugs, nanoparticles (NPs), or biomarkers. The applications of model cell membranes have extended beyond basic research, encompassing areas such as biosensing and nanoparticle camouflage to evade immune detection. In this review, we highlight advancements in the engineering of planar model cell membranes, focusing on the nanoarchitectonic tools used for their fabrication. We also discuss approaches for incorporating challenging materials, such as proteins and enzymes, into these models. Finally, we present our view on future perspectives in the field of planar model cell membranes.

Keywords: Langmuir; Langmuir–Blodgett; enzymes; model cell membranes; proteins; vesicle fusion.

Figure 6

(A) Injection of proteins or enzymes beneath the monolayer to promote their incorporation into the planar model cell membrane. (B) Transfer of the monolayer, incorporating proteins or enzymes, onto a solid support. Adapted with permission from [164]. Copyright 2014 American Chemical Society.

Figure 1

Timeline illustrating the development of various cell membrane models leading up to the currently accepted model. The last cartoon highlights current and future trends in the integration of extracellular structures into model cell membranes for diverse applications.

Figure 2

A simplified schematic diagram showing the composition of a cell membrane.

Figure 3

Timeline illustrating the most significant breakthroughs in the development of experimental planar model cell membranes.

Figure 4

Mechanism of bilayer formation through the vesicle fusion method. (A) Vesicles are adhered and adsorbed onto the substrate. (B) Vesicles fusion. (C) Induced stress between neighboring vesicles. (D) Rupture of the vesicles to form a lipid bilayer onto the solid substrate.

Figure 5

Illustrative plot of a Langmuir isotherm showing various phases and phase transitions typically observed in a surface pressure vs. area per molecule isotherm.

Figure 7

(Left, (A,B)) Langmuir–Blodgett and (right, (C)) Langmuir–Schaefer methodologies.

Figure 8

(A) Schematic representation of the natural binding of collagen fibers to the cell membrane via integrin proteins. (B) Chemical functionalization of a planar model cell membrane to incorporate collagen fibers, mimicking the natural cell membrane. Adapted with permission from [195]. Copyright 2010 American Chemical Society.