In the realm of biophysics, biotechnology, and related areas, understanding the intricate behaviors of lipid-based systems is of great interest. These systems, which include for example lipid monolayers, bilayers, and vesicles, serve as model membranes in various applications, from drug delivery to biosensor development. One of the most powerful tools for studying these systems is the Quartz Crystal Microbalance with Dissipation monitoring (QCM-D), which offers unparalleled insights into the formation dynamics and interactions of lipid-based systems on solid supports.
A seminal publication1 from 1998 by Keller and Kasemo showcased the power of QCM-D in analyzing lipid behavior at interfaces. Addressing lipid-surface interaction kinetics, i.e., how lipids interact with and arrange at three different types of surface materials, the paper demonstrated how QCM-D, like no other method at the time, directly and in real-time revealed whether the lipids formed a monolayer, a bilayer, or a layer of intact vesicles at the surface. This pioneering study, which remains a classic, illustrated the strengths of QCM-D in lipid-based research, and QCM-D has now been a standard technology in this field for more than two decades1.
So, what is QCM-D? Quartz Crystal Microbalance with Dissipation monitoring is a surface-sensitive, real-time analytical technology that measures changes in resonance frequency (f) and energy dissipation (D) of a quartz crystal sensor. These measurements provide detailed information about mass changes and viscoelastic properties of layers forming and residing at the sensor surface. Offering real-time information on mass, thickness, and viscoelastic properties of surface adhering layers, the QCM-D technology enables monitoring of interaction dynamics between lipids and the solid support. It also enables the characterization of the formed lipid-based structures.
Figure 1. QCM-D data revealing surface-specific vesicle interaction dynamics. By exposing three different surfaces, thiolated gold, SiO2, and oxidized gold, to small vesicles, the study1 demonstrated that the combination of frequency and dissipation unveils the dynamics of vesicle-surface interactions as well as the physical nature of the type of lipid assemblies that formed on the respective surface.
The key to being able to measure and detect structural changes, such as the vesicle rupture and fusion process, lies in the ability of QCM-D to measure what is often referred to as “hydrated mass”. Whereas the “dry mass”, measured by for example optical techniques, refers to the mass of the molecules of interest, the hydrated mass includes both the molecules and the associated solvent. Different structures and molecular assemblies trap different amounts of solvent, so monitoring the hydrated mass enables the detection of conformational changes, such as layer swelling and collapse, and the transition from vesicles to a bilayer. In these structural rearrangements, the number of molecules at the surface remains essentially the same, but the amount of coupled solvent differs.
In the analysis and characterization of lipid-based structures, this feature is very helpful as it enables the differentiation between for example lipids arranged as a vesicle and lipids arranged as a bilayer, where the former structure will have large amounts of associated solvent, and the latter will have little. The capability of QCM-D to reveal conformational changes and structural rearrangements in lipid-based systems, where different lipid assemblies trap different amounts of solvent, was demonstrated by the mentioned paper,1 which showed that (Fig. 1):
QCM-D technology is widely used in lipid-based research, offering insights into several key applications:
Today, there is a vast number of publications available on QCM-D analysis in lipid-related research. In addition to the paper by Keller and Kasemo that provided foundational insights that continue to influence current research, here is a handful of papers that could serve as a starting point to understand the power of QCM-D in lipid-based analysis. These studies have explored the formation of supported bilayers, how the formation is influenced by the ambient, and the interaction of lipid vesicles with various surfaces.
QCM-D technology has revolutionized the study of lipid-based systems, offering detailed, real-time insights into formation dynamics and interactions at solid support. As the field continues to evolve, the applications of QCM-D in lipid-based research are bound to expand, unlocking new possibilities and deeper understanding.
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Malin graduated in engineering physics in 2006, where her research focused on the QCM-D technology. Since then, she has been scrutinizing the how’s and why’s of the world in general, and the world of QCM-D in particular.
